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Y Koshino

Publications and source records attributed to Y Koshino.

At least 19 recordsLinked to original sources
PubMed2002

Apoptosis of astrocytes with enhanced lysosomal activity and oligodendrocytes in white matter lesions in Alzheimer's disease.

Cerebral white matter lesions in Alzheimer's disease (AD) consist of subcortical degeneration and ischaemic-hypoxic changes. Glial changes are intimately associated with the white matter lesions, and regressive changes in astrocytes and loss of oligodendroglial cells have been reported. We quantitatively compared glial changes including apoptosis and enhanced lysosomal activity in the frontal and temporal white matter by using terminal dUTP nick end labelling (TUNEL) and immunohistochemistry for glial markers, lysosomes and apoptosis-regulating proteins in non-familial AD brains. The degree of myelin pallor and axonal loss varied considerably in both the frontal and temporal white matter but fibrillary gliosis in demyelinated lesions tended to be less prominent in the temporal white matter in AD cases. A morphometric study with planimetric methods for cross-sectional areas of frontal and temporal white matter revealed that the white matter of AD cases manifested atrophy with significant reduction in frontal (11.9%) and temporal (29.4%) white matter compared to normal controls. Double immunolabelling for glial fibrillary acidic protein (GFAP) and KP1 (CD68) revealed KP1-positive fragmented structures within the weakly GFAP-labelled astrocytes. These KP1-positive structures correspond to process fragmentation and cytoplasmic vacuoles, which in turn indicate enhanced lysosomal activity during regressive changes in astrocytes. The KP1-modified astrocytes were not found in Pick's disease and corticobasal degeneration. The density of apoptotic glial cells, largely oligodendroglial, was significantly higher in the temporal than in the frontal white matter, and most GFAP-positive astrocytes with regressive changes were apoptotic. GFAP-positive astrocyte density was statistically the same in the frontal and temporal white matter, but the density of KP1-modified astrocytes was higher in the temporal than in the frontal white matter. The rate of white matter shrinkage was significantly correlated with the density of apoptotic glial cells and the density of KP1-modified astrocytes in the temporal lobe in AD cases. An increase in apoptotic glial cell density was found to contribute to GFAP-positive astrocytes with regressive changes in temporal white matter, while apoptosis of vascular smooth muscle cells did not show topographical accentuation. Astrocytes labelled with beta amyloid protein were not apoptotic, and the density of apoptotic cells labelled with CD95 and caspase-3 was too low in both types of white matter to be statistically evaluated. Our results imply that regressive changes in astrocytes and glial apoptosis are, to some extent, associated with white matter lesions, particularly of the temporal lobe in AD brains. The presence of apoptotic astrocytes with evidence of regressive change could therefore be a histological hallmark for white matter degeneration in AD.

Aged↗
PubMed2001

Overexpression of chlorophyllide a oxygenase (CAO) enlarges the antenna size of photosystem II in Arabidopsis thaliana.

The light-harvesting efficiency of a photosystem is thought to be largely dependent on its photosynthetic antenna size. It has been suggested that antenna size is controlled by the biosynthesis of chlorophyll b. To verify this hypothesis, we overexpressed the enzyme for chlorophyll b biosynthesis, chlorophyllide a oxygenase (CAO), in Arabidopsis thaliana by transforming the plant with cDNA for CAO under the control of the 35S cauliflower mosaic virus promoter. In the early de-etiolation phase, when the intrinsic CAO expression is very low, the chlorophyll a: b ratio was drastically decreased from 28 to 7.3, indicating that enhancement of chlorophyll b biosynthesis had been successfully achieved. We made the following observations in full-green rosette leaves of transgenic plants. (1) The chlorophyll a : b ratio was reduced from 2.85 to 2.65. (2) The ratio of the peripheral light-harvesting complexes (LHCII) to the core antenna complex (CPa) resolved with the green-gel system increased by 20%. (3) The ratio of the light-harvesting complex II apoproteins (LHCP) to 47-kDa chlorophyll a protein (CP47), which was estimated by the results of immunoblotting, increased by 40%. These results indicated that the antenna size increased by at least 10-20% in transgenic plants, suggesting that chlorophyll b biosynthesis controls antenna size. To the best of our knowledge, this is the first report on enlargement of the antenna size by genetic manipulations.

Apoproteins↗
PubMed2001

Nicotine-induced contraction in the rat coronary artery: possible involvement of the endothelium, reactive oxygen species and COX-1 metabolites.

Nicotine caused a contraction of the rat coronary artery in the presence of Nomega-nitro-L-arginine methyl ester (L-NAME) and arachidonic acid, and did not in the absence of these agents. The present experiments were undertaken to pharmacologically characterize the nicotine-induced contraction in ring preparations of the rat coronary artery. The contraction was abolished by chemical removal of endothelium saponin. Oxygen radical scavengers, superoxide dismutase and catalase, significantly attenuated the contraction. Cyclooxygenase-1 (COX-1) inhibitors (flurbiprofen, ketoprofen and ketrolack) attenuated the nicotine-induced contraction in a concentration-dependent manner, and cyclooxygenase-2 (COX-2) inhibitors at high concentrations (nimesulide and NS-389) slightly attenuated the contraction. A TXA2 synthetase inhibitor (OKY-046) attenuated the contraction to a small extent only at high concentrations. A TXA2 receptor antagonist (S-1452) attenuated the contraction in a concentration-dependent manner. A nicotinic receptor antagonist (hexamethonium) attenuated the contraction in part and an alpha-adrenoceptor antagonist (prazosin) nearly abolished the contraction. From these results, it was suggested that the contraction induced by nicotine in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium dependent, and involves reactive oxygen species and endothelial COX-1 metabolites of arachidonic acid. Part of the contraction is probably due to release of norepinephrine.

Animals↗
PubMed2000

Differentiation of Toxocara canis and T. cati eggs by light and scanning electron microscopy.

In this study, we investigated the morphological identification of Toxocara canis and T. cati eggs on the basis of light and scanning electron microscopic (SEM) observations. T. canis and T. cati eggs used in this study were recovered from the uteri of respective gravid female worms. Measurement of egg size was not helpful in the differentiation of these species, because approximately 90% of eggs measured were of similar size. Using SEM, we were able to differentiate T. canis eggs from T. cati eggs based on their respective characteristic surface structures. Both species have subspherical eggs with markedly pitted surfaces like those of a golf ball, but the surface pitting in T. canis is more coarse than that in T. cati. In this study, however, these differences were not absolute, as 16% of T. canis and 29% of T. cati eggs showed surface pitting that was uncharacteristic of their species. Of the 16% of T. canis eggs that could not be differentiated by surface structure, 3% had pitting resembling T. cati, and the remaining 13% showed intermediate type surface pitting. Similarly, 5% of T. cati eggs resembled T. canis, and 25% of these were of intermediate type. Light microscopic observation yielded results similar to those of SEM, indicating that light microscopy is also a useful tool for the identification of Toxocara eggs.

Animals↗
PubMed2000

Involvement of GABA(A) and GABA(B) receptors in afterdischarge generation in rat hippocampal slices.

It has been hypothesized that a disruption of gamma-aminobutyric acid (GABA) receptor-mediated processes may be involved in the pathophysiology of focal epilepsy. This disinhibition hypothesis has been postulated from the results of in vitro experiments of the interictal activity of focal epilepsy. Less is known, however, about how disinhibition may be involved in the production of the ictal activity. We therefore examined the pharmacological effects of selective agonists and antagonists of GABA(A) and GABA(B) receptors on ictal-like afterdischarges (ADs) induced following repetitive high-frequency electrical stimulation in the CA1 region of rat hippocampal slices. The GABA(A) receptor antagonist bicuculline (5 microM) fully blocked AD generation, as did the GABA(A) receptor agonist muscimol (2 microM), which is thought to produce a tonic inhibition during application. However, the benzodiazepine receptor agonist diazepam (5 microM), which enhances the inhibitory postsynaptic potential induced by synaptically released GABA, increased the number of spikes in the AD to 148.3% of the control value. On the other hand, the GABA(B) receptor antagonist phaclofen (1 mM) increased the number of spikes in the AD to 234.7% of the control value, while the GABA(B) receptor agonist baclofen (5 microM) reduced it to 46.9%. We therefore conclude that synaptic, but not tonic, activation of GABA(A) receptors appears to be necessary for ictal-like AD generation, while GABA(B) receptor activation plays a protective role. We therefore propose a modification to the simple disinhibition hypothesis.

Animals↗
PubMed2000

Regional cerebral blood flow in male schizophrenic patients performing an auditory discrimination task.

Regional cerebral blood flow (rCBF) was measured in 11 schizophrenic patients amid 10 normal controls, both at rest and while performing an auditory discrimination task. Single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was used for quantitative evaluation of rCBF. The schizophrenic patients showed greater rCBF in the temporal and parietal regions at rest than the controls, but no abnormalities were found in frontal perfusion. During task performance. on the other hand, the patients showed a reduced frontal rCBF. whereas there was no group difference in rCBF in the temporal and parietal regions. In addition, the left> right hemisphere asymmetries of rCBF observed in the controls during task performance were not present in the patients. although there was no group difference in hemisphere laterality in rCBF at rest. These findings suggest that the employment of a cognitive task for neuroimaging studies is useful for detecting abnormalities of brain activation. such as hypofrontality and altered hemisphere laterality. in patients with schizophrenia.

Adult↗
PubMed2000

An unusual case of rhythmic movement disorder.

Rhythmic movement disorder is one of the sleep-wake transition disorders listed in the International Classification of Sleep Disorders. According to this classification, the condition commonly occurs in infants and toddlers, and persistence beyond 4 years of age is unusual. Recently, we encountered a case in which rhythmic movement disorder persisted up until the age of 12 years with spikes registering on the sleep electroencephalogram. Epileptic seizure was ruled out because of the characteristic rolling movement, absence of any other epileptic symptoms (e.g. vocalization and tonic-clonic seizure) and cessation as a result of removal of the blanket.

Child↗
PubMed2000

Intratumoral pharmacokinetics of oligonucleotides in a tissue-isolated tumor perfusion system.

The intratumoral pharmacokinetics of model oligonucleotides were studied in Walker 256 tissue-isolated tumor preparations using an in situ single-pass vascular perfusion technique. A 20-mer phosphodiester (PO) oligonucleotide, its fully phosphorothioated (PS) oligonucleotide counterpart, and an 18-mer phosphorothioated oligonucleotide containing four 2'-O-methylribonucleosides at both the 3'-end and 5'-end (PS-OMe) were used. These oligonucleotides were administered to the tumor in two ways, by constant arterial infusion and by direct intratumoral injection. In the case of constant arterial infusion, the experiments were carried out using perfusate with or without 4.7% bovine serum albumin (BSA). The protein binding of PO, PS, and PS-OMe to BSA was 46%, 87%, and 94%, respectively. No marked difference was observed between the degree of accumulation of the three types of oligonucleotides in the tumor when BSA was present in the perfusate. PS and PS-OMe showed higher degrees of accumulation in tumors compared with PO when no BSA was present. These results indicate that free (i.e., protein unbound) PS-OMe and PS have superior tumor accumulation characteristics. In the intratumoral injection experiments, PS-OMe was retained longer in tumor tissue compared with PS, suggesting that it might be useful for direct local injection into solid tumors. Thus, the present study provides useful information about the basic disposition characteristics of oligonucleotides in solid tumors.

Animals↗
PubMed2000

Effects of scopolamine on interhemispheric EEG coherence in healthy subjects: analysis during rest and photic stimulation.

The present study of coherence analysis, in 16 healthy male volunteers, aged 24-31 years, showed that the administration of 0.25 mg of scopolamine significantly reduced interhemispheric coherence in the delta and beta-1 bands in the resting state. Scopolamine also caused a significant increase both in EEG coherence during PS and in PS-related coherence reactivity in the beta band. In addition, this compound significantly reduced total WMS scores. These findings suggest that, in addition to causing cognitive impairments, central cholinergic dysfunction can alter interhemispheric functional connectivity under both nonstimulus and stimulus conditions.

Adult↗
PubMed2000

Effect of normal aging upon interhemispheric EEG coherence: analysis during rest and photic stimulation.

The present study was conducted to examine and compare interhemispheric EEG coherence at rest and during photic stimulation (PS; 5, 10 and 15 Hz) in 30 younger subjects aged 22.1 +/- 2.2 (mean +/- S.D.) and 25 elderly subjects aged 56.8 +/- 4.9. The elderly subjects had significantly lower coherence in the resting EEG for the delta, theta, alpha-3, beta-1 and beta-2 frequency bands. In contrast, EEG analysis during PS showed that elderly subjects had significantly higher coherence in the frequency corresponding to PS at 15 Hz. In addition, when we examined the changes in coherence from the resting state to the stimulus condition (i.e., coherence reactivity), elderly subjects had significantly higher coherence reactivity to PS at 15 Hz. These findings suggest a low interhemispheric functional connectivity in elderly subjects under non stimulus conditions and a high connectivity during photic stimulus.

Adult↗
PubMed2000

Report of three cases of Alzheimer's disease with focal motor symptoms: clinical correlates of neuroimaging findings.

We report clinical and neuroimaging findings for three patients suffering from Alzheimer's disease (AD) with focal motor symptoms. These patients initially showed cognitive deficits and subsequently featured myoclonus and awkward movements in the unilateral upper limb while progressing to paresis. Paresis was noted in the unilateral upper limb. All patients held the unilateral arm flexed at the wrist and elbow, closely adducted to the body and the hand fisted and pronated. No signs of cerebellar ataxia, sensory disturbance or long tract signs were observed, nor any of the initial non-cognitive behavioural changes typical of frontotemporal dementia. EEGs of these patients showed marked slowing of basic activity without epileptic discharges. MRIs showed progressive brain atrophy in the contralateral frontoparietal lobes as well as the hippocampal formation. Cases 2 and 3 featured extensive long T2 lesions on MRI. 99mTc-HMPAO-SPECT revealed blood flow hypoperfusion in the corresponding regions. The cerebellum and brain stem showed neither morphological abnormalities nor blood flow hypoperfusion. On the basis of these clinical and neuroimaging observations, the focal motor symptoms were attributed to contralateral frontoparietal cortical atrophy with or without white matter lesion.

Aged↗
PubMed1999

Pindolol potentiates the effect of fluoxetine on hippocampal seizures in rats.

Recent studies have shown that behavioral and neurochemical changes induced by selective serotonin (5-HT) reuptake inhibitors such as fluoxetine are potentiated by coadministration of a 5-HT1A receptor antagonist. The present study assessed the effects of concomitant administration of fluoxetine and a 5-HT1A receptor antagonist, pindolol, on focal hippocampal (HIP) seizures elicited by electrical stimulation in rats. A 10 mg/kg dose of fluoxetine, which was ineffective by itself, produced a significant increase in the afterdischarge threshold of HIP seizures when combined with pindolol at 10 mg/kg. The inhibitory effect of this combination was eliminated by pretreatment with parachlorophenylalanine, a depletor of brain 5-HT. These findings suggest that treatments designed to increase 5-HT neurotransmission inhibit the generation of HIP seizures. A combination of fluoxetine with a 5-HT1A receptor antagonist could thus be therapeutically useful for the treatment of depressive symptoms in patients with epilepsy.

Animals↗
PubMed1999

Behavioral abnormalities and apoptotic changes in neurons in mice brain following a single administration of allylnitrile.

A single dose of allylnitrile in mice might induce persistent behavioral abnormalities, of which the mechanism is not yet known. The present study was undertaken to explore the relationship between behavioral abnormalities and pathological changes in the brain of mice following exposure to allylnitrile. Exposure to allylnitrile (63, 84, and 112 mg/kg, p.o.) resulted in dose-dependent changes in behavioral abnormalities, including increased locomotor activity, circling, retropulsion, head twitching, and alteration in reflexive behavior, which appeared at day 2 postdosing and were persistent throughout the experimental period (60 days) at the higher dose levels. Allylnitrile produced neuronal retraction including hyperchromasia of the nuclei in the raphe nuclei, cerebral cortex, hypothalamus, hippocampal CA1 and dentate gyrus later than 30 days. No gliosis was observed in these regions. Not all but a significant number of neurons in the hippocampal CA1, medial habenula and raphe nuclei were immuno-reactive to CPP32 (Caspase-3) even at day 2. These neurons were also positive to Hoechst 33258 staining, indicating allylnitrile caused apoptotic changes in specific neurons when neuronal behaviors became apparent. These apoptotic changes were persistent even in the area without neuronal contraction such as medial habenula. However, almost all neurons in these areas were also positive to terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL). It is conceivable that allylnitrile caused apoptotic changes in neurons but did not always lead them to cell death immediately. Moreover, even when neuronal contraction resulted in retention of behavioral abnormalities, onset of these abnormalities seems to be associated with the impairment in the habenulo-raphe relay due to activation of apoptotic cascade in neurons.

Animals↗
PubMed1999

The relationship between auditory ERP and neuropsychological assessments in schizophrenia.

To clarify the cognitive significance of event-related potential (ERP) abnormalities in schizophrenia, we examined the relationships of amplitudes and latencies of ERP components with performance on neuropsychological tests in schizophrenic patients. Twenty patients underwent the Trail Making B Test (TM-B), which is sensitive to frontal lobe dysfunction, and the logical memory, verbal paired-association, and visual reproduction subtests of the Wechsler Memory Scale (WMS), which are sensitive to temporal lobe dysfunctions, and ERP recordings during performance of an oddball auditory discrimination task. Pearson product-moment correlations indicated that an increased P200 amplitude was correlated with poor performance on the TM-B, whereas a decreased P300 amplitude was correlated with poor performance on the verbal paired-association subtest of the WMS. These findings suggest that a P200 abnormality represents the frontal lobe dysfunction, and a P300 abnormality represents the left temporal lobe dysfunction in schizophrenia.

Adolescent↗
PubMed1999

Epworth Sleepiness Scale and sleep studies in patients with obstructive sleep apnea syndrome.

Excessive daytime sleepiness (EDS) is the major symptom of patients with obstructive sleep apnea syndrome (OSAS). In this study, we examined the relationship between subjective EDS scored with the Epworth Sleepiness Scale (ESS), objective EDS measured with the multiple sleep latency test (MSLT) and sleep variables evaluated with polysomnography for patients with OSAS. Subjects were 10 patients (51.7+/-19.0 years old). The average ESS and MSLT scores were 10.6+/-5.6 and 7.7+/-5.6, respectively. There was no significant relationship between ESS and MSLT. The Multiple Sleep Latency Test had a significant negative relationship with the number of awakenings and the apnea/hypopnea index. No relationship was found between nocturnal hypoxia and either ESS or MSLT. Our findings suggest that objective EDS in OSAS is related with fragmentation of sleep, and that several patients are not aware of their EDS.

Adult↗