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Biomedical subjects

H Okazawa

Publications and source records attributed to H Okazawa.

At least 55 records · Page 3Linked to original sources
PubMed1997

Presenilin 1 binds to amyloid precursor protein directly.

Mutations in the presenilin genes are associated with early onset familial Alzheimer's disease and lead to accumulation of beta-amyloid peptide in the brain of patients, suggesting that presenilin abnormalities induce pathological processing of amyloid precursor protein (APP) in Alzheimer's disease. For the understanding of pathogenesis in this type of familal Alzheimer disease, it is important to know whether presenilins are directly involved in the metabolism of beta-amyloid or not. To test whether presenilin 1 (PS1) directly binds to APP, we performed two-hybrid interaction assays between these proteins in yeast cells by using bait plasmids for normal and mutant PS1 and prey plasmids for APP fragments corresponding to the different molecular portions. Positive interaction was observed in any combination between PS1 bait plasmids and APP prey plasmids. Therefore, our results show that PS1 binds to APP directly and suggest that the PS1 protein itself is involved in the metabolism of beta-amyloid peptide.

Alzheimer Disease↗
PubMed1997

Cortical processing mechanism for vocalization with auditory verbal feedback.

To investigate the relationship between motor and sensory speech center, cortical activity was examined using PET while normal subjects perceived their own voice which sounded different to the articulated one. The results showed significant activation in the superior temporal gyri with absence of activity in the supplementary motor area (SMA). In a previous study we found significant activation in SMA with no activity in the superior temporal gyrus when normal subjects simply vocalized. Thus, two different cortical pathways for vocalization were delineated: programmed pathway in SMA, and pathway with auditory verbal feedback. The former is thought to be the mature system in the adult, and the latter may be related to speech acquisition.

Adult↗
PubMed1997

The role of the temporal coding system in the auditory cortex on speech recognition.

To elucidate the temporal coding system for speech recognition, we synthesized stimulation sounds which do not contain formant information but do contain temporal information by transforming original sound wave to click sequences. Using this stimulation sound, we performed a recognition test and used PET to examine the cortical activities in normal subjects listening to this sound. The results of the recognition test showed a good perception of the sounds made from sequential speech. The PET study demonstrated significant activation of the superior temporal gyri while listening to the stimulation speech sounds. Our results imply that these stimulation sounds were processed semantically in the auditory cortices. The temporal processing system is thought to make an important contribution to speech recognition.

Adult↗
PubMed1997

Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c.

SNARE proteins have been implicated in the insulin-induced translocation of vesicles containing the GLUT4 glucose transporter to the plasma membrane of adipocytes. The role of the target SNARE SNAP-25 or its homologs in this process was investigated by screening a mouse adipocyte cDNA library with rat SNAP-25 and human SNAP-23 cDNA probes. Both positive clones isolated encoded a protein with 87% sequence identity to human SNAP-23, and which was therefore designated mouse SNAP-23. Immunoblot and immunofluorescence analyses revealed that SNAP-23 is located predominantly in the plasma membrane of 3T3-L1 adipocytes incubated in the absence or presence of insulin. Of syntaxins 1 to 5, SNAP-23 bound with the highest affinity to syntaxins 1 and 4 in the yeast two-hybrid system. Expression of SNAP-23, syntaxin 4, and the syntaxin-binding protein Munc 18c in COS cells revealed that Munc18c reduced the amount of SNAP-23 bound to syntaxin 4 in a concentration-dependent manner. These results suggest that the binding of SNAP-23 to syntaxin 4 is inhibited by Munc18c in adipocytes.

Adipocytes↗
PubMed1997

Presurgical identification of epileptic foci with iodine-123 iomazenil SPET: comparison with brain perfusion SPET and FDG PET.

Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15 min (early) and 3 h (late) after intravenous injection of 123I-IMZ (167 MBq). Parametric images of the ligand transport (K1) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers' input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.

Adult↗
PubMed1997

Cortical activation by monaural speech sound stimulation demonstrated by positron emission tomography.

To investigate how auditory input from each ear contributes to spoken language processing, cortical activation by monaural speech sound stimulation was examined in 12 normal subjects using 15O-labeled water positron emission tomography. Regional cerebral blood flow (rCBF) was measured under four different sound stimulation conditions: (1) silence, (2) white noise, (3) sequential Japanese sentences ("speech"), and (4) Japanese sentences played backward ("reversed speech"), and the results were evaluated by statistical parametric mapping (SPM). Noise induced significant rCBF increase in the contralateral Heschl's gyrus. Speech and reversed speech stimuli caused significant rCBF increase in the contralateral Heschl's gyrus and the bilateral superior temporal gyri, with contralateral activation broader than that in the ipsilateral hemisphere. Monaurally input speech sound signals that reach the contralateral Heschl's gyrus may be processed chiefly and phonologically in the surrounding superior temporal gyrus in the same hemisphere. Comparison of speech activation with reversed speech activation failed to demonstrate a significant difference, which made it difficult to identify the area for lexical and semantic processing.

Acoustic Stimulation↗
PubMed1997

[18F]-fluorodeoxyglucose-positron emission tomography findings in protein infants with severe periventricular leukomalacia and hypsarrhythmia.

UNLABELLED: Two preterm infants with extensive periventricular leukomalacia (PVL) were examined by [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) at the corrected ages of 18 and 34 days. They showed similar clinical courses including oculoclonic seizure, hypsarrhythmia and severe mental retardation, in addition, to spastic quadriplegia. FDG-PET study of these two infants with severe PVL disclosed poorly developed metabolic activity in the primary sensorimotor cortex, while the MRI images displayed only periventricular white matter lesions. CONCLUSIONS: Positron emission tomography may disclose cortical involvement in infants with severe periventricular leukomalacia.

Blood Glucose↗
PubMed1997

Sound-induced activation of auditory cortices in cochlear implant users with post- and prelingual deafness demonstrated by positron emission tomography.

Changes of regional cerebral blood flow (rCBF) in the auditory cortices induced by sound stimulation were examined in nine postlingually and five prelingually deaf cochlear implant (CI) users by 15O-labeled water Positron Emission Tomography, and the results were compared with those of eight normal volunteers. Speech stimulation caused significantly greater rCBF increase compared with noise stimulation in the auditory association area in normal and postlingually deaf subjects. In prelingually deaf subjects, however, speech activation of the auditory association area was much less than that found in either of the other two groups. Neuronal networks for speech sound processing in the auditory association area in postlingually deaf individuals are thought be similar to those in normal subjects, while those in prelingually deaf patients who received CI after the speech acquisition period may not develop completely.

Acoustic Stimulation↗
PubMed1997

[Primary cutaneous lymphoma--mycosis fungoides].

Malignant lymphoma of the skin is a type of extranodal lymphoma with a benign prognosis, in which the main organ involved is the skin. Some 80-90% of the cases in Japan show a T-cell phenotype. Mycosis fungoides and Sézary syndrome are common T-cell lymphomas of the skin. The tumor cells of mycosis fungoides, small and medium-sized cells with cerebriform nuclei, are detected in an epidermo-dermo junction. The tumor cells show CD3, CD4 and CLA, (cutaneous lymphocyte associated antigen) positivity. Various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA), and interferons, have been indicated for the good-risk group (stages I A, I B and II A). Electron-beam irradiation, various chemotherapy, such as low-dose etoposide, low-dose MTX and CPT-11 and deoxy coformycin (DCF) plus IFNs, have been indicated for intermediate-risk group (stage II B, III and IV A). BRMs plus low-dose etoposide, electron-beam irradiation and a multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, have been indicated for the high-risk group (stages IV A and IV B). Cutaneous B cell lymphoma (CBCL) can be diagnosed using a molecular biological assay. The tumor cells of CBCL do not express T-cell antigens such as CD2, CD3 and CD43 and show B-cell antigens such as sIg, CD19, CD20 and CD22. Electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). An effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, is required for patients with advanced stage CBCL (stages III and IV).

Antigens, CD↗
PubMed1996

Cortical speech processing mechanisms while vocalizing visually presented languages.

To elucidate cortical processing during vocalization, we used positron emission tomography to measure regional cerebral blood flow during vocalization in six Japanese subjects. During reading Japanese sentences used daily or short syllables aloud, the visual cortices, the left Heschl's gyrus, Broca's area, the primary motor area of the articulatory organs, the supplementary motor area and the cerebellum were significantly activated, compared with resting conditions. The superior temporal gyri were rarely activated. Significant activation of the cerebellum was observed by comparing cortical activity during reading sentences used daily with that during reading meaningless short syllables. These results suggest that vocalization of familiar materials is taken over by the cerebellum, rather than cortical speech areas, and without engagement of the superior temporal gyri.

Adult↗
PubMed1996

Regulation of striatal D1A dopamine receptor gene transcription by Brn-4.

Brn-4 is a member of the POU transcription factor family and is expressed in the central nervous system. In this study, we addressed whether Brn-4 regulates expression of the D1A dopamine receptor gene. We found a functional Brn-4 responsive element in the intron of this gene by means of cotransfection chloramphenical acetyltransferase assays. This region contains two consensus sequences for binding of POU factors. Gel mobility-shift assays using glutathione S-transferase-Brn-4 fusion protein indicated that Brn-4 binds to these sequences. Both these sites are essential for transactivation by Brn-4 because deletion of either significantly reduced this enhancer activity. In situ hybridization revealed colocalization of Brn-4 and D1A mRNAs at the level of a single neuron in the rat striatum where this dopamine receptor is most abundantly expressed. Gel mobility-supershift assay using rat striatal nuclear extract and Brn-4 antibody confirmed the presence of Brn-4 in this brain region and its ability to bind to its consensus sequences in the D1A gene. These data suggest a functional role for Brn-4 in the expression of the D1A dopamine receptor gene both in vitro and in vivo.

Animals↗
PubMed1996

POU transcription factors differentially regulate the D1A dopamine receptor gene in cultured cells.

Transcription is regulated by complex interactions between cis-elements and transcription factors. In this study, we found that members of the POU transcription factor family differentially regulate a cis-element of the human D1A dopamine receptor gene. The differences in transactivating abilities among POU factors are derived neither from their different binding affinities to the responsive element nor from their interaction with other types of transcription factors, suggesting the participation of coactivators. We also observed that POU family members, when expressed simultaneously, act competitively on this regulatory element. Our findings demonstrate that members of the same transcription factor family result in different outcomes in cultured cells. These observations suggest a novel model for in vivo gene regulation by different members of a transcription factor family through a single cis-element.

Base Sequence↗
PubMed1996

Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: the optimal scan time.

"Delayed" single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0-3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [123I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.

Alzheimer Disease↗
PubMed1996

Simplified quantification of regional cerebral blood flow with 99mTc-ECD SPECT and continuous arterial blood sampling.

The goal of this study was to develop a simple method for quantification of regional cerebral blood flow (rCBF) with 99mTc-ethyl cysteinate dimer (ECD) SPECT. Following an intravenous constant infusion of ECD for one minute, serial dynamic SPECT imaging was performed for 40 minutes in 6 healthy male volunteers with intermittent arterial blood sampling. PET scan with 15O-water was performed on the same day before the SPECT study for measurement of rCBF. Arterial blood data demonstrated rapid conversion of ECD to the hydrophilic metabolites, and most of the arterial input to the brain was completed within 5 minutes after the injection. Brain activity reached a peak value soon after the cessation of infusion, and was stable thereafter with very little washout. Net extraction of ECD in the brain calculated by arterial input of ECD and rCBF demonstrated a rapid decrease within a few minutes, reaching 42.7% at 5 minutes. The simulation study suggested that the arterial blood activity obtained by continuous drawing for 5 minutes and a single SPECT scan would provide a reasonable estimate of rCBF under the assumption of constant net extraction in the brain.

Adult↗
PubMed1996

Separation and determination of some stereoisomers by capillary gel electrophoresis with cyclodextrin incorporated in polyacrylamide gel.

Capillary gel electrophoresis (CGE) was successfully applied to the separation of optically active isomers and position isomers by incorporating a suitable cyclodextrin chiral selector in polyacrylamide gel. A commercially available ss-cyclodextrin (ss-CD) was used for enantioselectivity towards o-, m- and p-nitrobenzoic acid, o-, m- and p-hydroxybenzoic acid, o-, m- and p-toluic acid and the optical isomers of dansyl-D,L-leucine and R,S-1,1'-binaphthyl-2,2-dihydrogenphosphate. Especially the effect of organic solvents, such as acetonitrile, methanol, dimethylsulphoxide and others were examined in detail. The resolution varied to some extent with the addition of the organic solvent to the polyacrylamide gel and the running buffer solution. The possible mechanism has also been discussed. In addition, quantitative aspects of the separation of stereoisomers using CGE have been studied, showing that both the resolution and accuracy of the determinations were affected by the ratio of the enantiomers.

Journal Article↗