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Biomedical subjects

K Isaki

Publications and source records attributed to K Isaki.

At least 19 recordsLinked to original sources

Non-familial olivopontocerebellar atrophy combined with late onset Alzheimer's disease: a clinico-pathological case report.

A 76-year-old woman with olivopontocerebellar atrophy (OPCA) presented with progressive intellectual deterioration. She showed cerebellar ataxia and muscle atrophy and weakness, and gradually developed generalized dementia with visuospatial disturbance. An autopsy revealed numerous senile plaques (SPs), neurofibrillary tangles (NFTs) and neuropil threads particularly in the CA1, subiculum and entorhinal cortex and to a lesser degree in the cerebral neocortex shown by immunostaining and specific silver impregnation techniques. The nucleus basalis of Meynert had numerous NFTs with fibrillary gliosis and neuronal cell loss. The basis pontis was markedly atrophied and the pontine nucleus had severe neuronal depopulation and gliosis. The pontine transverse fibers were demyelinated with their axons being fragmented. The cerebellar white matter was also severely degenerated. The striatum, Onuf's and intermediolateral nuclei of the spinal cord remained unchanged. Ubiquitin immunohistochemistry and Gallyas silver impregnation technique revealed oligodendroglial inclusions in the pontine nucleus, corticopontine tract, cerebral and cerebellar white matter. On double immunostaining of KP1 and ubiquitin, globular neurite SPs encircled by KP1-positive fibrous structures were found in the hippocampus and cerebral neocortex. The curly neurite SPs contained KP1-positive granules. The KP1-positive microglial cells were distributed widely in the cerebral white matter and HLA-DR-positive ones were found around the SPs. The present case showed generalized dementia compatible with Alzheimer's disease (AD) and had a pathologically limbic type of late onset AD. This is the first case where AD affected non-familial OPCA.

Aged

The effect of neuronal perturbation on the uptake of [18F]2-fluoro-2-deoxy-D-glucose in brain slices of the rat.

The positron-emitting radionuclide 18F was used to label 2-fluoro-2-deoxy-D-glucose producing [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG), and subsequently applied to sagittally-sectioned brain slices of the rat to evaluate the activity of neurons for up to 7 h in living brain slices. The amount of [18F]FDG uptake, which is proportional to the activity of neurons, was monitored every 20 min in five representative brain regions: frontal cortex, caudate-putamen, thalamus, hippocampus and cerebellum. The uptake of [18F]FDG linearly increased with time in these areas, showing constant glucose utilization. The rate of uptake was reversibly decreased by tetrodotoxin (TTX) regardless of brain region, but some uptake was insensitive to TTX. There was a tendency for the uptake to be decreased in Ca2+-free, 5 mM Mg2+ (2 mM EGTA) solution, suggesting some remaining functional synapses. Thus in sagittally-sectioned brain slices, most glucose metabolism is dedicated to neuronal firings and some metabolism to synaptic activities and to other functions of neurons and glial cells. When Cd2+ was applied to brain slices at 0.1-1 mM, the curve of [18F]FDG uptake irreversibly declined, indicating its toxic effect rather than its blocking action of transmitter release at synapses. The cerebellum was the most sensitive to Cd2+, and the caudate-putamen was the least sensitive. The present method, therefore, can be also used as a rapid examination system for checking neurotoxicity of substances.

Action Potentials

Alcohol effect on sleep electroencephalography by fast Fourier transformation.

The influence of alcohol (ethanol) on sleep was investigated in 10 men. Polysomnography (PS) was recorded on a baseline night (BL-N) and an ethanol (0.8 g/kg) night (Et-N). On visual score rapid eye movement (REM) sleep was reduced, REM latency was prolonged on Et-N as compared to BL-N. Using the fast Fourier transformation method, electroencephalographic power density of REM sleep in delta frequencies band and in the 10-12 Hz range of non-REM sleep were enhanced. REM sleep and non-REM sleep changes were prominent in the second-half and first-half of the night, respectively.

Adult

Mitral valve prolapse and autonomic function in panic disorder.

We investigated the significance of mitral valve prolapse (MVP) and autonomic function in 121 patients diagnosed with panic disorder (PD). The incidence of MVP was higher in these patients (32.2%) than in the healthy controls (16.7%), but the difference was not significant. In the group with PD accompanied by depression, the MVP rate was 58.1%, significantly higher than the value of 25.7% observed in the PD patients without depression. The severity of MVP was mild; nearly all of the cases were silent, without cardiac murmur, and there was no problem with the left ventricular function. The coefficient of variation for R-R intervals on electrocardiograms (CV R-R) was smaller in patients with PD than in healthy controls. The CV R-R of PD patients was significantly lower in the group with MVP than in the group without MVP, suggesting a strong association with the parasympathetic nervous system. Since the CV R-R tended to decrease in the presence of depression, involvement of the parasympathetic nervous system was inferred.

Adolescent

Nocturnal melatonin profiles before and one year after beginning shift-work.

Nocturnal serum melatonin profiles were determined twice for seven single women, during their time of employment as nurses (baseline), and after one year (follow up), in order to investigate the effects of shift-work on nocturnal melatonin secretion. All subjects were working in the same hospital under an irregularly rotating three-shift system. Five (5) mL blood samples were drawn six times at 2 h intervals between 20:00-06:00 hours under dim light conditions (< 50 lux). The same sampling procedures were repeated the following year. The results showed pronounced inter-individual differences in melatonin concentrations. There was a trend towards increasing maximum melatonin concentration (MAX melatonin) at follow up, with a similar tendency seen in summed melatonin (the sum of six measured melatonin concentrations). A trend was also seen towards increasing melatonin ratio at 06:00 hours (the percentage of melatonin concentration at 06:00 hours by summed melatonin) at follow up. Melatonin concentration at 06:00 hours was significantly higher at follow up, and a significant correlation between Morningness-Eveningness score (M-E score) at baseline and increased summed melatonin at follow up was also seen. These results suggest that: nocturnal melatonin secretion does not significantly increase after beginning shift-work; and that greater increases in melatonin secretion at follow up are found in subjects with higher M-E scones (increased morning type). With more subjects, however, there may be significant increase in MAX melatonin and/or summed melatonin in the follow-up study.

Adult

Neurons and extracellular neurofibrillary tangles in the hippocampal subdivisions in early-onset familial Alzheimer's disease: a case study.

We have investigated morphometrically unaffected neurons, intracellular neurofibrillary tangles (I-NFT) and extracellular neurofibrillary tangles (E-NFT) in eight subdivisions of the hippocampal cortex in two cases of early-onset familial Alzheimer's disease (FAD) and six cases of early-onset sporadic Alzheimer's disease (SAD). The hippocampal subdivisions examined included: CA4, CA3, CA2, CA1, prosubiculum, subiculum and presubiculum (PRE), parasubiculum (PARA) and entorhinal cortex (ENT). CA3, CA2 and CA1 in the FAD cases showed more severe neuronal loss and much greater E-NFT formation than in the SAD cases, while ENT in both the FAD cases showed less neuronal loss and less E-NFT formation. These data suggest that the cornu ammonis is affected more severely than the ENT in the FAD cases. These observations indicate that hippocampal pathology in the FAD cases is qualitatively as well as quantitatively different from that in sporadic cases. These results provide further evidence for pathological heterogeneity in AD, although the number of FAD cases examined is very small.

Aged

Pathology of the cerebellar dentate nucleus in sporadic olivopontocerebellar atrophy: a morphometric investigation.

The pathology of the cerebellar dentate nucleus was investigated by morphometric methods in three patients with sporadic olivopontocerebellar atrophy (sOPCA), and the results were compared to specimens from three subjects without neurological disease (controls). The size of dentate neurons; the number of small and large neurons (50-199 microns2 and larger than 200 microns2, respectively) at rostral, middle, and caudal levels; nerve cell density; total volume of the gray band; and total nerve cell number, were estimated with an image analyzer applied to serial 20-microns-thick sections of one celloidin-embedded cerebellar hemisphere. The number of small neurons in patients with sOPCA was significantly increased at the rostral level while the number of large neurons showed large inter-individual variations. Dentate neurons also showed various qualitative changes such as atrophy and hypertrophy. The nerve cell density in the dentate nucleus was 1.7 times higher in the patients than in the controls. However, the total volume of the gray band was reduced to one-half of that in controls. There were no differences in the total nerve cell number between the patients and controls. This reduction in size of the dentate gray matter in patients with sOPCA may result from the disappearance of afferent nerve fibers originating from Purkinje cells, inferior olivary neurons, and pontine neurons.

Aged

Neurons, intracellular and extracellular neurofibrillary tangles in subdivisions of the hippocampal cortex in normal ageing and Alzheimer's disease.

Unaffected neurons, intracellular neurofibrillary tangles (I-NFTs) and extracellular NFTs (E-NFTs) in six normal subjects and six patients with Alzheimer's disease (AD) were morphometrically evaluated in eight subdivisions of the hippocampal cortex, using the Gallyas silver impregnation technique modified by the application of hematoxylin and eosin. The subdivisions examined included CA1-4, prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and the entorhinal cortex (ENT). In the AD patients, the number of unaffected neurons in ENT, CA1, PRO and PARA was significantly decreased to one-quarter to two-thirds of that of the normal aged subjects. These four subdivisions in the AD patients had a greater number of both I- and E-NFTs. There were no significant differences in the total number of unaffected neurons, I- and ENTs between the AD patients and normal aged subjects for all the subdivisions. These findings suggest that neuronal loss in the hippocampal cortex in AD is almost entirely due to NFT formation. Furthermore, with regards to neuronal loss and NFT formation, there were two different subdivision groups in the AD patients. One group was composed of severely affected subdivisions (ENT, CA1, PRO and Para) and was distinct from the other group which was composed of mildly affected subdivisions (CA4, CA3, CA2 and PRE). Each subdivision in the normal aged subjects belonged to the mildly affected group as seen in the AD patients. These findings indicate that both neuronal loss and NFT formation associated with normal ageing and with AD are not only quantitatively but also qualitatively different.

Aged

Quantitative EEG in never-treated schizophrenic patients.

To clarify whether patients with schizophrenia still show EEG slowing in the absence of psychopharmacological treatment, EEG was analyzed in 20 acute never-treated schizophrenics and 20 age-matched healthy controls using the computerized wave-form recognition method. Compared to controls, schizophrenics had more fast theta (6-8 Hz) and slow alpha (8-9 Hz) activity, and less fast alpha activity (9-13 Hz). The average EEG frequency at O1 correlated negatively with total and positive symptom scores on the BPRS in the schizophrenic group. These findings confirm that the frequency of alpha rhythm is slowed in schizophrenia and that this slowing is possibly related to the expression of psychopathology in this disorder.

Adult

Serial proton magnetic resonance spectroscopy in a patient with the interval form of carbon monoxide poisoning.

Serial proton magnetic resonance spectroscopy (1H-MRS) studies were performed from immediately after the appearance of sequelae in a patient with the interval form of carbon monoxide (CO) poisoning. The volume of interest was set over the frontal lobe white matter. In the early period a persistent increase in choline was found, which was thought to reflect the course of progressive demyelination. The appearance of lactate and decrease in N-acetylaspartate reflected the point at which neuron injury became irreversible. These were followed later by the finding of irreversible changes on MRI and single photon emission computed tomography. The findings suggest that 1H-MRS may be a useful modality to determine neuron viability and prognosis early in the course of the interval form of CO poisoning.

Brain Diseases

In vivo proton magnetic resonance spectroscopy study on premature aging in adult Down's syndrome.

Proton magnetic resonance spectroscopy (1H-MRS) was performed in a group of 18 adult patients with Down's syndrome (DS) aged 20-46 years, and the peak area ratios (NAA/Cr, Cho/Cr, NAA/Cho) of N-acetylaspartate (NAA), total creatine (Cr), and choline-containing compounds (Cho) calculated separately in the patients in their 20's, 30's, and 40's. In age-matched healthy control groups, there were no significant age-related changes in any of the peak area ratios. In contrast, in the DS group, although the relative amount of NAA (NAA/Cr) showed no significant change with increasing age, the relative amount of Cho (Cho/Cr and NAA/Cho) was significantly increased in the 40's group. At least as judged by MRI, few age-related general morphological changes such as brain atrophy were apparent in the third, fourth, and fifth decade groups. However, the MRI findings considered together with the age-related changes in the peak area ratios suggest that in DS patients in the fifth decade metabolic abnormalities such as degradation and/or rapid synthesis of brain cell membrane may occur prior to neuronal loss and degeneration.

Adult

Frontal intermittent delta activity in schizophrenic patients receiving antipsychotic drugs.

FIRDA was found in 14 EEGs recorded from 338 schizophrenic patients receiving antipsychotic drugs, although they showed no FIRDA in the baseline EEG. The daily dose of antipsychotic drugs when FIRDA was found was larger than when FIRDA disappeared. FIRDA was assumed to be induced by relatively high doses of antipsychotic drugs. Thus, the effect of antipsychotic drugs should be added to the list of differential diagnoses associated with FIRDA. FIRDA did not correlate with the baseline psychopathology of schizophrenic patients. Patients without FIRDA tended to respond poorly to antipsychotic drugs in terms of negative symptoms. Improvement of positive symptoms in FIRDA patients was not as remarkable as in patients without FIRDA.

Adolescent

The influence of light drowsiness on the latency and amplitude of P300.

Light drowsiness affected the P300 obtained with a standard auditory oddball paradigm. A simple two-tone discrimination paradigm was used. The frequent nontarget stimuli were 1000 Hz pure tones and the infrequent target stimuli were 2000 Hz pure tones. The subjects were required to press a button whenever infrequent target tones were presented. With light drowsiness, P300 increased in latency and decreased in amplitude, but the counts of infrequent tones remained correct nevertheless. It was concluded that electrophysiological brain function differs in the light drowsy and awake states. In studies on P300, it is essential to rule out light drowsiness to obtain valid P300 amplitudes and latencies.

Adult

A survey of tardive dyskinesia in psychiatric inpatients in Japan.

To investigate the prevalence of tardive dyskinesia (TD) in a group of psychiatric patients receiving low doses of antipsychotic drugs, we examined 647 Japanese inpatients (361 men and 286 women) with a mean age of 49.8 years, receiving a mean dose of antipsychotic drugs of 276.8 mg of chlorpromazine equivalent. TD was diagnosed according to the criteria of Schooler and Kane with the Abnormal Involuntary Movement Scale. The overall prevalence of TD was 22.3%. Mild TD was found in 67.4% of TD patients, moderate TD in 29.2%, and severe TD in 3.5%. The TD patients were older (59.0 years) than those without this condition (47.2 years). The prevalence of TD increased with advancing age until the 7th decade, when it reached a plateau. The dose of daily antipsychotic drugs was lower in the TD patients (207.6 mg) than in the patients without TD (296.6 mg). The duration of primary illness was longer in the TD patients (28.9 years) than in the patients without TD (20.4 years). Patients receiving antiparkinsonism drugs showed TD less frequently (20.7%) than those not receiving such drugs (31.0%). No significant associations were found between the presence of TD and sex or primary illness.

Adolescent