Biomedical subjects

Tohru Sawada

Publications and source records attributed to Tohru Sawada.

28 records · Page 2Linked to original sources

PubMed2004

APP, NGF & the 'Sunday-driver' in a Trolley on the Road.

Alzheimer's disease (AD) is one of the most common and challenging neurodegenerative diseases in humans and is characterized by: progressive impairment in cognitive function, degeneration of cholinergic neurons of the basal forebrain (CBF), neurofibrillary tangles and amyloid beta-peptide (Abeta) depositions. The amyloid precursor protein (APP) is a transmembrane protein of which abnormal processing produces Abeta that is associated with the pathogenesis of AD. Neurotrophic factors have attracted much attention for their potential as a remedy for neurological disorders. In this regard, nerve growth factor (NGF) has generated a great interest as a potential target for the treatment of AD. This interest is based on the observation that CBF neurons, which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus, undergo selective and severe degeneration in advanced AD and that the survival of CBF neurons depends upon NGF and its receptors, namely, trkA and p75NTR. This review focuses on recent findings about APP, NGF and their potential signaling-connections to the protein encoded by the 'Sunday-driver' (SYD) gene.

Alzheimer Disease↗

PubMed2003

Evaluation of two-dimensional L-COSY and JPRESS using a 3 T MRI scanner: from phantoms to human brain in vivo.

Localized versions of two-dimensional (2D) magnetic resonance spectroscopic (MRS) sequences, namely JPRESS and L-COSY, have been implemented on a whole-body 3T MRI/MRS scanner. Volume selection was achieved using three slice-selective radio-frequency (RF) pulses: 90 degrees-180 degrees-180 degrees in JPRESS and 90 degrees-180 degrees-90 degrees in L-COSY with a CHESS sequence prior to voxel localization for global water suppression. The last 180 degrees RF pulse was used for resolving the J-coupled cross peaks in JPRESS, whereas the last 90 degrees RF pulse was used for coherence transfer between J-coupled metabolites in L-COSY. A head MRI coil for 'transmission' and a 4 inch receive surface coil for 'reception' or a head coil transmit/receive were used. A total of 16 healthy volunteers were investigated using these 2D MRS sequences. Voxel sizes of 18 and 27 ml were localized in the occipito-parietal gray and white matter regions and the total duration for each 2D signal acquisition was typically 35 min. Compared with 2D L-COSY, reduced spectral width along the second spectral dimension and shorter 2D spectral acquisition were the major advantages of 2D JPRESS. In contrast, increased spectral width along the new spectral dimension in L-COSY resulted in an improved spectral dispersion enabling the detection of several brain metabolites at low concentrations that have not been resolved using the conventional one-dimensional (1D) MRS techniques. Due to increased sampling rate, severe loss of metabolite signals due to T2 during t1 was a major drawback of 2D JPRESS in vivo.

Adult↗

PubMed2003

Vascular cognitive impairment.

Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.

Cerebrovascular Disorders↗

PubMed2003

Activation of the anterior cingulate gyrus by 'Green Odor': a positron emission tomography study in the monkey.

The equivalent mixture of cis-3-hexenol and trans-2-hexenal (hexenol/hexenal), 'green odor', is known to have a healing effect on the psychological damage caused by stress. Behavioral studies in humans and monkeys have revealed that hexenol/hexenal prevents the prolongation of reaction time caused by fatigue. In the present study, we investigated which brain regions are activated by the odor of hexenol/hexenal using positron emission tomography with alert monkeys. Regional cerebral blood flow (rCBF) in the prepyriform area (the primary olfactory cortex) was commonly increased by the passive application of odor: acetic acid, isoamylacetate or hexenol/hexenal. We observed rCBF increases in the orbitofrontal cortex (the secondary olfactory cortex) by these olfactory stimuli in two of three monkeys, and found no predominance of laterality of the activated hemisphere. Furthermore, rCBF increase in the cerebellum was observed in two of three monkeys, and the odor of acetic acid increased rCBF in the substantia innominata in all monkeys. In addition to these olfactory related regions, the anterior cingulate gyrus was activated by the odor of hexenol/hexenal. These findings suggest that the increase of rCBF in the anterior cingulate gyrus by the odor of hexenol/hexenal may contribute the healing effects of this mixture observed in the monkey.

Aldehydes↗

PubMed2002

The 3' untranslated region of the new rat synaptic vesicle protein 2B mRNA transcript inhibits translational efficiency.

Post-transcriptional regulatory mechanisms have been shown to play a major role in gene expression in eukaryotic cells. Sequences within the 3'-untranslated region (3'UTR) of mRNAs have been described as being important for enhancing or inhibiting message translation. Using fluorescence microscopy, Western blotting and the reverse transcription-polymerase chain reaction (RT-PCR) method, we demonstrate that the 3'UTR of the new rat transcript of synaptic vesicle protein 2B (SV2Bb) mRNA is involved in post-transcriptional regulation of SV2Bb translation. When fused to a reporter gene, this 3'UTR markedly inhibited protein synthesis in transiently transfected cells and this decreased translational efficiency did not occur through changes in mRNA stability. In conclusion, our study gives new insights into unraveling the molecular mechanisms involved in the post-transcriptional regulation of the SV2B gene.

3' Untranslated Regions↗

PubMed2002

Proton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer's disease.

To investigate metabolic changes in Alzheimer's disease (AD), we performed proton MR spectroscopy at 3T Spectra were acquired from the gray matter of the posterior cingulate gyrus and the precuneus, and from the parietooccipital white matter in nine AD patients and 12 controls. In patients, the N-acetyl group (NA)/creatine + phosphocreatine (Cr) ratios were decreased in both regions, and a decrease in the glutamate + glutamine (Glx)/Cr ratio and a correlation between the NA/Cr and Glx/Cr ratios were detected in the gray matter, but not in the white matter. These results suggest that NA and Glx metabolism are simultaneously affected in AD, however, metabolic changes in Glx are more profound in the gray matter than in the white matter.

Aged↗

PubMed2002

Characterizing CGI-94 (comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain.

The treatment of Alzheimer's disease (AD) remains a major challenge because of the incomplete understanding of the triggering events that lead to the selective neurodegeneration characteristic of AD brains. Here we describe a new protein, CGI-94, that is down-regulated at the mRNA level in the hippocampus of early stage AD brain. Transfection experiments with CGI-94 as a green fluorescent protein (GFP)-fusion-protein show that this protein is translocated into the nucleus of the cell. The finding that this protein, which has a bipartite nuclear localization signal, is also observed in the cytoplasm and extracellular space points to a multifunctional protein. Immunohistochemical analyses reveal that CGI-94 is mainly expressed in neurons of the hippocampal formation and the cortex but not in the cerebellar nucleus. In conclusion, the expression of the nucleolar phosphoprotein CGI-94 appears to be disturbed in early processes of neuronal degeneration.

Aged↗

PubMed2002

Functional anatomy of chemical senses in the alert monkey revealed by positron emission tomography.

Functional imaging technique using positron emission tomography (PET) has made it possible to localize functional brain regions in the human brain by detecting changes in regional cerebral blood flow (rCBF). Performing PET studies in the monkey will aid in integrating monkey electrophysiological research with human PET studies. We examined changes in rCBF during olfactory or combined olfactory and gustatory (flavour) stimulation using PET in the alert rhesus monkey. Olfactory or flavour stimulation with acetic acid or apple increased rCBF in the prepyriform area, substantia innominata and amygdala. Besides these areas, flavour stimulation increased rCBF in the anterior insula and frontal operculum, orbitofrontal cortex, inferior frontal gyrus and cerebellum. Apple odour or flavour stimuli increased rCBF in the inferior occipital gyrus in addition to the above areas. These findings suggest that the increases of rCBF in response to neural activities in the primary olfactory and gustatory cortices are detectable by the use of PET. In addition, regions activated by apple stimuli suggest that higher brain function might be detected with PET in the alert monkey.

Animals↗

PubMedDate not supplied

Involvement of microtubule integrity in memory impairment caused by colchicine.

In order to fully evaluate the effects of colchicine treatment on learning ability in rats, colchicine was administered, and both Morris water maze (MWM) and step-through type passive avoidance (PA) learning tests were conducted. In both learning tests, infusion of colchicine into the rat dentate gyrus, at two distinct bilateral rostrocaudal locations, potently impaired memory function in a dose-dependent manner (0.01-2.0 microg/site), whereas systemic injection of colchicine (50-300 microg/kg) did not. In the MWM test, memory impairment was observed even at doses where there was no evidence of any histological changes in the dentate granule cells. This suggests that functional deterioration, that is, learning impairment was induced by the dysfunction of microtubules and/or axons, was caused by colchicine. Moreover, ameliorated learning behavior was observed with chronic treatment of beta-estradiol 3-benzoate, which has been suggested to have an important role as an adjuvant treatment for younger Alzheimer's disease (AD), immediately after colchicine infusion (0.3 microg). These results indicate that the animal model accompanying the colchicine-induced functional defect showing early tau pathology, but not neuronal cell degeneration, may well mimic comparatively early stage of AD.

Alzheimer Disease↗

PubMedDate not supplied

Highly diffusion-sensitized tensor imaging of unilateral cerebral arterial occlusive disease.

BACKGROUND AND PURPOSE: Selective neuronal death is a well-recognized histopathologic sequel to moderate ischemic brain damage. However, radiologic visualization of these changes has not been established, even with diffusion tensor imaging (DTI). We sought to determine whether DTI with b values > or =1900 s/mm(2) reveals occult diffusion abnormalities in patients with cerebral arterial occlusive disease. METHODS: Six patients (five men, one woman; mean age +/- standard deviation, 66 +/- 8 years) with unilateral internal carotid or middle cerebral arterial occlusive disease but not parenchymal T2 hyperintensity underwent 3T fast DTI with b < or = 1300 s/mm(2) and slow DTI with b > or = 1900 s/mm(2). We postprocessed mean diffusibility and fractional anisotropy (FA) images from the fast and slow DTI datasets. Standardized asymmetry indices (AIs) were used to identify regional asymmetries. Diagnostic accuracy among the DTI modalities was assessed by means of receiver operating characteristic analysis. RESULTS: In hemispheres ipsilateral to occluded vessel, AIs were significantly elevated on fast mean-diffusibility images of white matter at the levels of the internal capsule (95% confidence interval [CI]: 1.00, 1.09; P = .045) and corona radiata (95% CI: 1.01, 1.12; P = .034). AIs were significantly decreased on slow FA images at the internal capsule (95% CI: 0.84, 0.98; P = .018) and white matter at the internal capsule level (95% CI: 0.92, 1.00, P = .043). The slow FA map had the highest accuracy (89.8%) for detecting the hemisphere ipsilateral to arterial occlusion. CONCLUSION: Slow FA maps acquired by using DTI with high b values are useful for visualizing ischemic brain damage in apparently normal WM.

Aged↗