Biomedical subjects

K Isaki

Publications and source records attributed to K Isaki.

At least 19 recordsLinked to original sources

PubMed2000

Neuronal loss and neurofibrillary degeneration in the hippocampal cortex in late-onset sporadic Alzheimer's disease.

To explore more fully the relationship between neuronal death and neurofibrillary degeneration, unaffected neurons, intracellular neurofibrillary tangles (i-NFT) and extracellular NFT (e-NFT) in 22 patients with late-onset sporadic Alzheimer's disease (AD) were morphometrically evaluated in eight subdivisions of the hippocampal cortex, using the Gallyas hematoxylin-eosin stain. The subdivisions examined included CA4, CA3, CA2, CA1 (CA: cornu ammonis), prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and the entorhinal cortex (ENT). The unaffected neuron density was significantly lower and both i-NFT and e-NFT densities were significantly higher in subdivisions other than CA4 and CA3 in AD patients compared with those in the aged controls. Unaffected neuron density was significantly, inversely correlated with e-NFT density and with total NFT density in all subdivisions except for PRE in AD patients. Especially in CA2, CA1, PRO and ENT, there were strong correlations between the neuron density and these NFT densities. Both unaffected neuron and e-NFT densities in CA1 and ENT were significantly correlated with the disease duration. The i/e-NFT ratio, an index of the degree and/or rate of progress of neuronal death via neurofibrillary degeneration, showed the lowest value in ENT in AD patients. The findings suggest that neuronal death via neurofibrillary degeneration starts earliest and/or most rapidly progresses in ENT. Furthermore, the i/e-NFT ratios in both ENT and CA1 were significantly correlated with the disease duration, suggesting that the neuronal death pattern in the two subdivisions parallels disease progression.

Age Factors↗

PubMed2000

[Balloon-occluded retrograde transvenous obliteration (B-RTO) for portal hypertension].

We reviewed the current techniques and published results of balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) and hepatic encephalopathy. The portal hemodynamics of gastric varices were classified into three types according to their feeding vessels, and the development of collateral veins under balloon occlusion of gastro-renal shunt was classified into five grades. The main draining veins of gastric varices were gastro-renal and gastro-inferior phrenic shunts. Preprocedural diagnosis of portal hemodynamics is important in selecting the technique for B-RTO. The rate of disappearance or marked reduction of GV was 98%, and the rate of recurrence of GV was 2%. Hepatic encephalopathy due to gastro-renal shunt improved markedly. In contrast, esophageal varices were aggravated at rates of 10% to 62.5% by the post-procedural elevation of portal pressure. Common adverse effects were hemoglobinuria, abdominal pain, and low-grade fever, but ascites and pleural effusion were also reported. Severe complications such as cardiogenic shock, atrial fibrillation, and pulmonary embolism were reported. We await technical improvements and further indications for this procedure.

Catheterization↗

PubMed1999

Dynamic changes in glucose metabolism induced by thiamine deficiency and its replenishment as revealed by a positron autoradiography technique using rat living brain slices.

Dynamic changes in the cerebral glucose metabolic rate (CMRglc) before and after thiamine replenishment were investigated in living brain slices obtained from pyrithiamine-treated (PT) and pair-fed control rats by use of a positron autoradiography technique. Fresh rat brain slices (300 microm thick) were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, during which serial two-dimensional images of [18F]FDG uptake in the slices were constructed on the imaging plates. The net influx constant (=K) of [18F]FDG was determined by a Patlak graphical method of the image data. Prior to thiamine pyrophosphate (TPP)-loading, the K value in the neurologically symptomatic PT was higher in all brain regions except the thalamus and mammillary body than the control, suggesting compensatory enhanced glycolysis. The rapid decrease in this heightened net influx constant immediately after TPP-loading was surmised to be due to activation of pyruvate oxidation with lactate as the substrate, with this inhibiting the glycolysis. From > or = 150 min after TPP-loading, the K value continued to show low values in the thalamus and mammillary body, which are regarded as the responsible sites for Korsakoff syndrome, whereas in all other sites recovery to control values was observed. These findings suggest that using this technique the quantitative evaluation of serial local changes in CMRglc from thiamine deficiency to after its replenishment may be useful in elucidating the pathophysiology and prognosis of Wernicke's encephalopathy.

Animals↗

PubMed1999

Neuronal substrates participating in attentional set-shifting of rules for visually guided motor selection: a functional magnetic resonance imaging investigation.

To investigate the neuronal substrates participating in attentional set-shifting for motor selection rules, a functional magnetic resonance imaging study was performed during hand-shape selection tasks. During the session, six right-handed subjects were required to make one of three hand-shapes using their right hands, in response to the hand-shape images on a video screen, following one of the three predefined rules of win, lose, and tie. The selection rules were consistently applied in three conditions (win, tie, and lose), and changed alternately in one condition (alternate win-lose). Thus the alternate win-lose condition requires the shift of rules for motor selection. This alternate condition compared with the win, tie, and lose conditions showed activation in the left middle frontal gyrus, the bilateral inferior frontal gyri, and the left posterior fusiform and lingual gyri. These activation patterns in the prefrontal cortex were similar to those observed during the performance of the Wisconsin Card Sorting Test (WCST), which requires a typical set-shifting ability from one perceptual dimension to another (Berman et al., 1995. Neuropsychologia 33, 1027-1046; Nagahama et al., 1996. Brain 119, 1667-1675; Konishi et al., 1998. Nature Neuroscience 1, 80-84.). Our data may indicate that the dorsolateral prefrontal cortex including the middle and inferior frontal gyri are important in attentional set-shifting of both perceptual and non-perceptual characteristics. Another activation in the fusiform and lingual gyri may have reflected the increased attentional demand for visual processing in the light of a current rule for motor selection.

Adult↗

PubMed1999

Non-linear analysis of the sleep EEG.

A sleep electroencephalogram was analyzed by non-linear analysis. The polysomnography of a healthy male subject was analyzed and the correlation dimensions calculated. The correlation dimensions decreased from the 'awake' stage to sleep stages 1-3 and increased during rapid eye movement (REM) sleep. These results were seen during each sleep cycle. In each sleep cycle, the correlation dimensions decrease for slow wave sleep, and increase for REM sleep.

Adult↗

PubMed1999

Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia.

A 26-year-old Japanese woman slowly developed a change of character such as hypospontaneity and blunted affect, followed by obvious mental deterioration. She was diagnosed as having a disorganized type of schizophrenia at the first examination. Brain magnetic resonance imaging demonstrated diffuse high intensity in the cerebral white matter, particularly in the frontal lobes. The single photon emission computed tomography images using 123I-IMP disclosed diffuse cerebral hypofusion, especially in the frontal lobes. Electroencephalogram showed a moderate amount of 5-6Hz theta waves on the background of alpha activity. Nerve conduction velocities in the extremities were delayed. The level of leucocyte arylsulphatase was low. In the arylsulphatase A gene analysis, a compound heterozygote having the 99Gly-->Asp and 409Thr-->Ile mutations was confirmed. The patient was diagnosed as having metachromatic leukodystrophy. She gradually showed obvious dementing symptoms such as memory disturbance and disorientation. The characteristics of the psychiatric symptoms in the leukodystrophy are discussed.

Adult↗

PubMed1998

Clinical studies on three cases of the interval form of carbon monoxide poisoning: serial proton magnetic resonance spectroscopy as a prognostic predictor.

Three patients with the interval form of carbon monoxide (CO) poisoning were studied for associations between their clinical courses and serial changes on: (1) MRI; (2) EEG; (3) single photon emission computed tomography with N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP SPECT); and (4) proton magnetic resonance spectroscopy ([1HIMRS) to evaluate their usefulness as prognostic predictors. A hyperintense area on MRI T2-weighted images and a hypointense area on T1-weighted images, appearing in the deep white matter, persisted for a prolonged period even after improvement of the clinical symptoms, and did not become an accurate indicator of clinical evaluation or prognosis. [1H]MRS studies with the volume of interest set in the frontal lobe white matter revealed increases in choline-containing compounds, and reductions of N-acetylaspartate in all cases. These findings normalized in one subclinical case over time. Distinctive findings in the severe cases included increased lactate in two cases showing akinetic mutism, with a difference in prognosis noted according to the degree and period of persistence of this increase. EEG findings were relatively well correlated with clinical symptoms in the early period, with a good correlation no longer consistent after a certain period was exceeded. [123I]IMP SPECT findings did not always reflectclinical symptomatology either. These results indicate that [1H]MRS is the most useful indicator in the clinical evaluation of patients with the interval form of CO poisoning.

Adult↗

PubMed1998

Dynamic changes in glucose metabolism by lactate loading as revealed by a positron autoradiography technique using rat living brain slices.

To demonstrate the preference of lactate over glucose as an energy substrate in normal brain tissue under normoxic condition, the dynamic changes in glucose uptake by lactate loading were investigated in living rat brain slices using a positron autoradiography technique. Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution containing 10 mM glucose at 36 degrees C. During incubation, serial two-dimensional imaging of [18F]FDG uptake in the slices was constructed on the imaging plates. Lactate loading (20 mM) reversibly suppressed the [18F]FDG accumulation up to 80 min. Compared with the pre-loading and the unloaded control values, [18F]FDG uptake was suppressed to 25-45% in cerebral regions and 6-7% in cerebellum. The lactate concentration in the surrounding medium decreased after lactate loading. Hence brain tissue preferentially uses lactate over glucose under normoxic and euglycemic condition.

Animals↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Effect of flunitrazepam on sleep and memory.

Flunitrazepam's (FNZ) effect on sleep and memory 1 mg and 2 mg was investigated in 6 healthy volunteers (mean age 21.5 +/- 0.8 years) by polysomnography (PSG) and memory testing. A PSG was recorded on each study night. Memory testing was done before sleep (40 min after taking FNZ or placebo), and after waking (560 min after medication). Rapid eye movement (REM) latency was found to be prolonged on the FNZ 2 mg night (FNZ2N) compared to the baseline night (BN). Percentage of stage 2 sleep was increased in the FNZ2N as compared to BN, while REM percentage on both FNZ nights did not significantly differ from BN. The number of total REM and REM density were decreased in the FNZ2N compared to BN. Memory testing showed significant differences between before sleep and after waking on the FNZ2N. There was a significant correlation between the degree of impairment on memory testing and the rate of reduced REM density, but there was no significant correlation between degree of impairment on memory testing and the rate of increased non-REM sleep on the FNZ2N. The results of this study suggest that impairments in memory result from the dose of FNZ, and that there is a possibility of a relationship between memory disturbance and REM sleep suppression caused by this benzodiazepine.

Adult↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Echocardiographic evaluation of cardiac valvular abnormalities in adults with Down's syndrome.

It is well known that congenital heart abnormalities are common in children with Down's syndrome. However there are few studies on cardiac abnormalities in adults with Down's syndrome. Therefore, we estimated cardiac abnormalities by means of echocardiography in 30 institutionalized Japanese adults with Down's syndrome, but without cardiac symptoms. Two-dimensional echocardiography showed an incidence of 26.7% in mitral valve prolapse and 20% increase of echo brightness in the mitral valve. Doppler echocardiography revealed an incidence of 16.7% in mitral valve regurgitation, and 13.3% in aortic valve regurgitation. Thus, even adults with Down's syndrome who are apparently free of cardiac symptoms may be at risk for valvular disease.

Adult↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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↗

PubMed1995

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↗