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Biomedical subjects

Takashi Asada

Publications and source records attributed to Takashi Asada.

At least 19 recordsLinked to original sources

Changes in hippocampal GABABR1 subunit expression in Alzheimer's patients: association with Braak staging.

Alterations in the gamma-aminobutyric acid (GABA) neurotransmitter and receptor systems may contribute to vulnerability of hippocampal pyramidal neurons in Alzheimer's disease (AD). The present study examined the immunohistochemical localization and distribution of GABA(B) receptor R1 protein (GBR1) in the hippocampus of 16 aged subjects with a range of neurofibrillary tangle (NFT) pathology as defined by Braak staging (I-VI). GBR1 immunoreactivity (IR) was localized to the soma and processes of hippocampal pyramidal cells and some non-pyramidal interneurons. In control subjects (Braak I/II), the intensity of neuronal GBR1 immunostaining differed among hippocampal fields, being most prominent in the CA4 and CA3/2 fields, moderate in the CA1 field, and very light in the dentate gyrus. AD cases with moderate NFT pathology (Braak III/IV) were characterized by increased GBR1-IR, particularly in the CA4 and CA3/2 fields. In the CA1 field of the majority of AD cases, the numbers of GBR1-IR neurons were significantly reduced, despite the presence of Nissl-labeled neurons in this region. These data indicate that GBR1 expression changes with the progression of NFT in AD hippocampus. At the onset of hippocampal pathology, increased or stable expression of GBR1 could contribute to neuronal resistance to the disease process. Advanced hippocampal pathology appears to be associated with decreased neuronal GBR1 staining in the CA1 region, which precedes neuronal cell death. Thus, changes in hippocampal GBR1 may reflect alterations in the balance between excitatory and inhibitory neurotransmitter systems, which likely contributes to dysfunction of hippocampal circuitry in AD.

Adenosine Triphosphatases↗

Brain magnetic resonance imaging and single photon emission computerized tomography findings in a case of relapsing polychondritis showing cognitive impairment and personality changes.

A 57-year-old female with relapsing polychondritis (RP) showing CNS complications is described with reference to the MRI and SPECT findings. At the age of 56, the patient was diagnosed with RP based on her symptoms, which included bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, and ocular inflammation, as well as vestibular dysfunction. During the course of the disease, she suffered from aseptic meningitis accompanied by delirium, which was resolved by treatment with cyclophosphamide, in addition to prednisolone concurrent with the improvement of her physical condition. After the meningitis improved, she developed a number of cognitive impairments, including time disorientation, agraphia, acalculia, constitutional apraxia, and personality changes. Simultaneously, we observed, via SPECT, a decrease in cerebral blood flow (CBF) in several regions, including the bilateral frontal, lateral temporal, and parietal regions. This is the first study to report on the CNS manifestations of RP with reference to MRI and SPECT findings.

Brain Mapping↗

EEG filtering based on blind source separation (BSS) for early detection of Alzheimer's disease.

OBJECTIVE: Development of an EEG preprocessing technique for improvement of detection of Alzheimer's disease (AD). The technique is based on filtering of EEG data using blind source separation (BSS) and projection of components which are possibly sensitive to cortical neuronal impairment found in early stages of AD. METHODS: Artifact-free 20s intervals of raw resting EEG recordings from 22 patients with Mild Cognitive Impairment (MCI) who later proceeded to AD and 38 age-matched normal controls were decomposed into spatio-temporally decorrelated components using BSS algorithm 'AMUSE'. Filtered EEG was obtained by back projection of components with the highest linear predictability. Relative power of filtered data in delta, theta, alpha 1, alpha 2, beta 1, and beta 2 bands were processed with Linear Discriminant Analysis (LDA). RESULTS: Preprocessing improved the percentage of correctly classified patients and controls computed with jack-knifing cross-validation from 59 to 73% and from 76 to 84%, correspondingly. CONCLUSIONS: The proposed approach can significantly improve the sensitivity and specificity of EEG based diagnosis. SIGNIFICANCE: Filtering based on BSS can improve the performance of the existing EEG approaches to early diagnosis of Alzheimer's disease. It may also have potential for improvement of EEG classification in other clinical areas or fundamental research. The developed method is quite general and flexible, allowing for various extensions and improvements.

Aged↗

Genetic and expression analyses of FZD3 in schizophrenia.

BACKGROUND: Wnt signaling plays important roles in neurodevelopmental processes. Frizzled is a receptor of Wnt protein, and the Frizzled 3 (FZD3) gene was recently reported to be associated with schizophrenia. Our study attempted to confirm associations between FZD3 and schizophrenia in Japanese family and case-control samples. METHODS: Genetic associations were evaluated using family-based transmission tests (212 families, 643 subjects) and case--control analysis (540 schizophrenia patients, 540 control sample). Six single nucleotide polymorphisms (SNPs) on the FZD3 locus were genotyped, and levels of FZD3 mRNA expression in postmortem brains were examined. RESULTS: Neither family- nor population-based studies supported associations between FZD3 and schizophrenia. FZD3 expression was unaltered in schizophrenic brains. CONCLUSIONS: Although two prior studies have reported associations using limited numbers of SNPs on FZD3, our intensive study failed to support any major contribution of FZD3 to schizophrenia susceptibility.

Adult↗

GABAA receptor gamma subunits in the prefrontal cortex of patients with schizophrenia and bipolar disorder.

Immunohistochemical and immunoblot techniques were employed in order to examine alterations of the GABAA receptor gamma subunits in the prefrontal cortex from postmortem subjects with schizophrenia and bipolar disorder. Immunohistochemically, gamma 1/3 immunolabeling in the neuronal soma in the prefrontal cortex from subjects with bipolar disorder was more intense than that of the controls and the subjects with schizophrenia. The intensity of gamma 1/3 immunolabeling of the schizophrenic subjects was comparable with that of the controls. Immunoblot analysis demonstrated a significant increase in the gamma 1 subunit in the bipolar subjects, whereas no remarkable difference was detected in the schizophrenic subjects. The present study suggests that the GABAA receptor gamma subunit is differentially involved in schizophrenia and bipolar disorder, and that the gamma subunit is up-regulated in the prefrontal cortex of subjects with bipolar disorder.

Adult↗

Effects of partial volume correction on discrimination between very early Alzheimer's dementia and controls using brain perfusion SPECT.

We assessed the accuracy of brain perfusion single-photon emission computed tomography (SPECT) in discriminating between patients with probable Alzheimer's disease (AD) at the very early stage and age-matched controls before and after partial volume correction (PVC). Three-dimensional MRI was used for PVC. We randomly divided the subjects into two groups. The first group, comprising 30 patients and 30 healthy volunteers, was used to identify the brain area with the most significant decrease in regional cerebral blood flow (rCBF) in patients compared with normal controls based on the voxel-based analysis of a group comparison. The second group, comprising 31 patients and 31 healthy volunteers, was used to study the improvement in diagnostic accuracy provided by PVC. A Z score map for a SPECT image of a subject was obtained by comparison with mean and standard deviation SPECT images of the healthy volunteers for each voxel after anatomical standardization and voxel normalization to global mean or cerebellar values using the following equation: Z score = ([control mean]-[individual value] )/(control SD). Analysis of receiver operating characteristics curves for a Z score discriminating AD and controls in the posterior cingulate gyrus, where a significant decrease in rCBF was identified in the first group, showed that the PVC significantly enhanced the accuracy of the SPECT diagnosis of very early AD from 73.9% to 83.7% with global mean normalization. The PVC mildly enhanced the accuracy from 73.1% to 76.3% with cerebellar normalization. This result suggests that early diagnosis of AD requires PVC in a SPECT study.

Aged↗

Association between tau polymorphism and male early-onset Alzheimer's disease.

Neurofibrillary tangles, containing hyperphosphorylated microtubule-associated protein tau, are one of the major pathological hallmarks of Alzheimer's disease. To investigate a possible association between tau genotypes and the risk of Alzheimer's disease, we screened for polymorphisms in the tau gene and found a novel polymorphism IVS11 + 90G --> A. A case-control study (874 patients and 678 controls) showed a significant association between possession of the A allele and male Alzheimer's disease with early-onset (age of onset before 65, odds ratio = 2.65; 95% confidence interval 1.30-5.42), suggesting that age and gender modify the risk effect. However, we failed to replicate the reported association between the Saitohin gene located in the tau intron 9 and Japanese Alzheimer's disease.

Adult↗

Immunohistochemical and immunoblot study of GABA(A) alpha1 and beta2/3 subunits in the prefrontal cortex of subjects with schizophrenia and bipolar disorder.

A number of investigations have provided a growing body of evidence of the involvement of the gamma-aminobutyric acid (GABA) transmitter system in the pathophysiology of schizophrenia and bipolar disorder. In this study, immunohistochemical and immunoblot techniques were employed in order to examine alterations of the GABA(A) receptor alpha1 and beta2/3 subunits in the prefrontal cortex from postmortem subjects with schizophrenia and bipolar disorder. alpha1 immunoreactivity was observed in the neuropil of the prefrontal cortex and in the neuronal soma in specimens from both groups, as well as from normal controls. alpha1 immunolabeling in the neuronal soma from the schizophrenic group was more intense than that of the other two groups. The distribution of beta2/3 immunoreactivity was similar to that of alpha1. beta2/3 immunolabeling in the neuronal soma from the schizophrenia and bipolar disorder groups was more intense than that of the normal controls. The densitometry measurements, as well as the immunoblot analysis for alpha1 and beta2/3 were highly consistent with the alpha1 and beta2/3 immunohistochemistry results. The present study suggests that the expression of these two GABA(A) receptor subunits was altered in subjects with schizophrenia and bipolar disorder, but that the patterns of change differed between those with these two disorders.

Adult↗

Immunohistochemical study of hnRNP B1 in the postmortem temporal cortices of patients with Alzheimer's disease.

In order to examine the post-transcriptional regulations in Alzheimer's disease, we employed immunohistochemical techniques and examined the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 in the inferior temporal cortex of subjects with Alzheimer's disease. In the mild cases, intense B1 immunoreactivity was observed in neurons of layer V, and less intense immunoreactivity was observed in layers II and III. The overall distributions and intensities of B1 immunoreactivity were undistinguishable among mild, moderate, and severe cases. Double-immunolabeling with MC1 and B1 demonstrated that B1 immunoreactivity was preserved in the majority of neurofibrillary tangle (NFT)-bearing neurons. Our study suggests that hnRNP B1-associated post-transcriptional regulations are preserved in the inferior temporal cortex of Alzheimer's disease.

Aged↗

A case of neurosyphilis showing a marked improvement of clinical symptoms and cerebral blood flow on single photon emission computed tomography with quantitative penicillin treatment.

A 31-year-old woman manifested significant emotional symptoms and personality change due to neurosyphilis; her clinical symptoms were improved with quantitative penicillin treatment. On admission, magnetic resonance imaging (MRI) showed no abnormal findings, while N-isopropyl-p-[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT) initially showed a remarkable increase in cerebral blood flow (CBF) in the cerebral cortex. This increase disappeared after improvement of the patient's clinical symptoms with treatment. It appears that the increase in CBF might have reflected an active inflammatory state of neurosyphilis and that its disappearance might therefore represent successful treatment with penicillin for neurosyphilis. Our case study suggests that single photon emission computed tomography (SPECT) is a useful method for evaluating an inflammatory state and for assessing the effect of therapy on neurosyphilis.

Adult↗

Gender difference in brain perfusion 99mTc-ECD SPECT in aged healthy volunteers after correction for partial volume effects.

BACKGROUND: Previous reports have yielded controversial results concerning gender differences in regional cerebral blood flow (rCBF). To elucidate this issue, we compared 99mTc ethyl cysteinate dimer single photon emission computed tomography (SPECT) images for brain perfusion between aged-matched healthy men and women after correction for partial volume effects (PVEs). METHODS: Brain perfusion SPECT in the resting state was performed on 40 healthy, right-handed subjects, 20 men and 20 women, with an age range of 58-86 years, who did not differ sociodemographically. PVE correction was performed using grey matter volume measured by magnetic resonance imaging. Statistical parametric mapping was used for the analysis of the adjusted rCBF images of relative flow distribution. RESULTS: The PVE correction revealed that women had higher rCBF in left inferior frontal gyrus, bilateral middle temporal gyri, and left superior temporal gyrus. Men had higher rCBF in left superior frontal gyrus, right medial frontal gyrus, right superior parietal lobule, right postcentral gyrus, right cerebellum, right middle frontal gyrus, right fusiform gyrus, and right precuneus. CONCLUSION: Significant gender differences in rCBF existed in these healthy volunteers. The PVE correction of SPECT images revealed gender differences that were consistent with the universal findings of better performance on verbal tasks in women and on visuospatial tasks in men.

Aged↗

Ion chromatographic determination of ammonia in air using a sampling tube of porous carbon.

The ion chromatographic determination of ammonia in air using a sampling tube of porous carbon carbonized at 500 degrees C was examined. When the mean recovery and the reproducibility for a series of five determinations were examined for 1 and 10 ppm ammonia gases, the mean recovery (n = 5) and the relative standard deviation were 97.0% and 3.5% for 1 ppm and 86.9% and 2.8% for 10 ppm, respectively. Furthermore, the recovery from 10 ppm ammonia gas increased with an increase in the extraction time, and a recovery of 99.7% was obtained for 180 min of extraction time. The mean collection efficiency for 1 and 10 ppm ammonia gas was 102.5% and 96.5%, respectively. The relation between the sampling volume and the peak area was linear, and the linearity was 0.999 of the correlation coefficient. The ammonia gas concentration in an actual goat shed could be determined by this sampling device for a sampling volume of 5 L at a flow rate of 1 L/min; 0.79 ppm of the determination value practically agreed as compare with 0.78 ppm from collection by a boric acid solution.

Journal Article↗

[Behave-AD].

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Activities of Daily Living↗

Superiority of 3-dimensional stereotactic surface projection analysis over visual inspection in discrimination of patients with very early Alzheimer's disease from controls using brain perfusion SPECT.

UNLABELLED: In Alzheimer's disease (AD), regional cerebral blood flow (rCBF) in the posterior cingulate gyri and precunei has been reported to decrease even at a very early stage. It may be helpful to use statistical image analysis to distinguish slight decreases in rCBF in this area. We compared a 3-dimensional stereotactic surface projection (3D-SSP) technique with visual inspection in the discrimination of patients with very early AD from age-matched controls using brain perfusion SPECT. METHODS: SPECT was obtained in 38 patients with probable AD at a very early stage and after a mean interval of 15 mo and in 76 age-matched healthy volunteers. We randomly divided these subjects into 2 groups. The first group was used to identify the areas with significant decreases of rCBF in patients compared with healthy control subjects based on the voxel-based analysis using 3D-SSP. The second group was used to compare the discrimination ability between patients and control subjects by 3D-SSP with that by visual inspection. In the second group, a Z-score map for a SPECT image of a subject was obtained by comparison with mean and SD SPECT images of control subjects for each voxel after anatomic standardization and voxel normalization to reference regions. Receiver operating characteristic (ROC) curves for a Z-score discriminating patients with AD from control subjects were analyzed in areas with significant decreases of rCBF identified in the first group. For visual inspection, 6 physicians graded the rCBF decrease on SPECT images for ROC curves. They inspected the images twice at an interval of >2 wk, and intra- and interobserver reliabilities were determined. RESULTS: Visual inspection showed fair-to-excellent intra- and interobserver reliabilities. The 3D-SSP demonstrated an accuracy of 86.2% for discriminating patients with AD from control subjects when analyzing the posterior cingulate gyri and precunei with global mean normalization. In contrast, visual inspection did not show an accuracy of >74.0% for this discrimination. CONCLUSION: The ability of 3D-SSP to discriminate patients with very early AD from control subjects is superior to that of visual inspection. It is clinically useful and reliable to adopt the use of 3D-SSP as an adjunct to visual interpretation.

Aged↗

[A psychopathological study on three-dimensional computer graphics (3DCGs): special reference to pictures made by a schizophrenic patient before and after the onset].

A patient with catatonic type schizophrenia drawing 3-dimensional computer graphics (3DCGs) before and after the onset is reported. His 3DCGs are discussed from the view of psychopathology. A 21-year-old male was admitted to our hospital. He was an art student. For three months before admission, he had been absorbed in drawing 3DCGs. When he was asked to draw handmade pictures by his teacher, he experienced a bizarre mood and took an overdose of aspirin. At the time of admission, he was in a stupor state, and was diagnosed with catatonic type schizophrenia. After admission, he exhibited excitement and disorganized speech. These symptoms disappeared after administration of neuroleptics, and he was discharged. The 3DCGs he drew before and after the onset revealed several special characteristics. First, the compositions of his pictures were too geometric and too precise. Secondly, the themes of his pictures changed from romantic before the onset to symbolic after it, and the styles changed from realistic to abstractive after the onset. Finally, histograms of the 3DCGs revealed many colors before onset, which converged to simple colors after. Therefore, it was suggested that the latent pathological process at the beginning of schizophrenia might be reflected in his 3DCGs. 3DCGs are a new type of fine art. They can express beautiful and cool images more simply than handmade pictures. Due to these features, artists can create images of their innerworld, with less effort and talent than picture drawings, by computer assistance. This case suggests that the geometric working space, change-free viewpoints, and computer assistance, which are characteristics of the methods in making 3DCGs may be suitable for schizophrenic artists to create images of their innerworld. However, being absorbed in making 3DCGs could also promote the latent schizophrenic process to the onset.

Adult↗