Biomedical subjects

R Okeda

Publications and source records attributed to R Okeda.

At least 37 records · Page 2Linked to original sources

PubMed1998

Mitochondrial encephalomyopathy showing prominent microvacuolation and necrosis of intestinal smooth muscle cells: a case diagnosed by rectal biopsy.

A 40-year-old woman who developed intestinal dysmobility was found, at rectal biopsy, to have marked microvacuolation of mucosal muscle layer cells, which corresponded to increased accumulation of abnormal mitochondria. Skeletal muscle biopsy specimens showed ragged-red fibers, vessels strongly reactive for succinic dehydrogenase, and focal deficiency of cytochrome c oxidase. Autopsy performed at the age of 50 revealed prominent accumulation of abnormal mitochondria in the intestinal smooth muscle cells with a mottled distribution of focal necrosis, multiple small cerebral infarcts with diffuse neuronal loss, and rarefaction of the perivascular white matter. Mitochondrial DNA analysis showed a point mutation at position 3243. This case, showing features of both mitochondrial neurogastrointestinal encephalomyopathy and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), indicates that routine intestinal biopsy can detect mitochondrial encephalomyopathy with gastrointestinal involvement. The main intestinal changes were extensive accumulation of abnormal mitochondria in the leiomyocytes and scattered focal necrosis.

Female↗

PubMed1998

Study on the etiopathogenesis of multiple spongy necrosis of the pontine base in three autopsy cases.

The etiopathogenesis of multiple spongy necrosis (MSN) of the pontine base was analyzed by examining the spatial relationship with intra- and extrafascicular vascular structures by reconstruction of serial sections of nine lesions from three autopsy cases. All nine lesions in the fascicles were distributed without any spatial relationship to the intrafascicular vessels. Instead, these lesions were distributed in parallel with arterial and venous transverse main branches between the anteromedial and anterolateral groups of the pontine vessels. On the other hand, all lesions in the middle cerebellar peduncle were arranged obliquely along the arterial and venous main trunks of the lateral group vessels with sparing of the perivascular narrow zone of the white matter. Moreover, narrow fascicles, even though located in the dorsomedial region of the pontine base, which is consistently involved in MSN, were spared, and thick transverse and longitudinal fascicles were selectively involved. The marginal zone of fascicles was spared, and focal coagulation necrosis was sometimes found in MSN lesions. Additionally, normal fascicles did not have their own nutritional arteries, and were nourished by arterioles and capillaries from the surrounding pontine gray matter. Neither severe organic stenosis nor occlusion of pontine vessels was found. On the basis of the close topographical relationship of MSN lesions with the pontine vascular architecture in addition to preferential involvement of thick fascicles with sparing of the marginal zone and inclusion of focal coagulation necrosis, it is proposed that the etiopathogenesis of MSN is pontine ischemia on a background of the characteristic parenchymal and vascular architecture of the pontine base. As to the cause of the ischemia, it is proposed that some functional disorder such as arterial vasoconstriction in the pontine base or the vertebrobasilar artery is responsible, rather than organic changes in the vessels.

Adenocarcinoma↗

PubMed1998

Delayed recovery of cortical auditory evoked potentials and blood flow precede cortical neuronal death after transient cerebral ischemia in gerbils.

Cortical neurons develop into neuronal death four days after transient cerebral ischemia. The aim of this study is to detect early post-ischemic changes in the cortex that will develop into cortical neuronal death later. The detection is important for starting adequate treatment within the therapeutic window. We have examined changes in middle-latency auditory evoked potentials (MAEPs) and cortical blood flow (CBF) in relation to the histological changes in the auditory cortex of Mongolian gerbils subjected to transient cerebral ischemia. At 2 min after bilateral carotid occlusion, the amplitude of MAEPs and CBF were reduced to 22.2 to 23.4% and 24.3 to 27.4% of the pre-ischemic level, respectively. In the 4-min ischemia group, the amplitude of each parameter recovered rapidly to the pre-ischemic level. In the 12-min ischemia group, the recovery of MAEPs and CBF was delayed by, from 20 to 30 min, and about 10 min, respectively. Also, scattered eosinophilic neurons were observed in the auditory cortex, and a mild but significant decrease in the number of surviving neurons was also detectable. The recovery of MAEPs in both groups was characterized by the appearance of a transient high amplitude (2.67 +/- 0.6 microV) low frequency (62.2 +/- 3.4Hz) wave. The present findings show that cortical neuronal death in the auditory cortex, which results from transient cerebral ischemia in the gerbil, is predictable by detecting the delay in the recovery of MAEPs amplitude and CBF during the very early post-ischemic phase. Clinical data is mandatory for the application of the presented method in clinical cases to save many patients with acute cerebrovascular diseases in the future.

Animals↗

PubMed1998

Astrocytes containing amyloid beta-protein (Abeta)-positive granules are associated with Abeta40-positive diffuse plaques in the aged human brain.

Amyloid beta-protein (Abeta) is the major component of senile plaques that emerge in the cortex during aging and appear most abundantly in Alzheimer's disease. In the course of our immunocytochemical study on a large number of autopsy cases, we noticed, in many aged nondemented cases, the presence of unique diffuse plaques in the cortex distinct from ordinary diffuse plaques by immunocytochemistry. The former were amorphous, very faintly Abeta-immunoreactive plaques resembling diffuse plaques, but they stained for Abeta40 and were associated with small cells containing Abeta-positive granules. A panel of amino- and carboxyl-terminal-specific Abeta antibodies showed that such Abeta40-positive diffuse plaques and cell-associated granules were composed exclusively of amino-terminally deleted Abeta terminating at Abeta40, -42, and -43. Double immunostaining also showed that those Abeta-immunoreactive granules are located in astrocytes and not in microglia or neurons. Immunoelectron microscopy revealed that nonfibrillar Abeta immunoreactivity was located within lipofuscin-like granules in somewhat swollen astrocytes. These findings raise the possibility that astrocytes take up Abeta and attempt to degrade it in lysosomes in the aged brain.

Adult↗

PubMed1998

Quantitation of amyloid beta-protein (A beta) in the cortex during aging and in Alzheimer's disease.

In this study we sought to learn about when and how amyloid beta-protein (A beta) accumulates in the cortex of normal individuals and about the difference in the A beta accumulation between normal aged and Alzheimer's disease (AD) brains. From consecutive autopsy cases and AD cases, hippocampus CA1 and occipitotemporal cortex T4 were sampled for A beta quantitation by the well characterized two-site enzyme immunoassays (EIAs). There was a strong tendency toward A beta 42 accumulation between the ages of 50 and 70 years in T4 and a little later in CA1. The A beta 42 levels were consistently higher in T4 than those in CA1 in any given case. The levels of A beta 42 in AD brains were significantly higher than those in control brains, and the extent of A beta 42 amino-terminal modification was also much greater in AD brains than that in control brains. Even in cases in which no senile plaques were immunocytochemically detected, EIAs clearly showed that significant amounts of A beta 42 already had accumulated. In contrast to A beta 42, A beta 40 showed no apparent age-dependent accumulation, and its high levels were found to be associated with AD.

Adult↗

PubMed1998

Histopathological and morphometric study of the late effects of heavy-ion irradiation on the spinal cord of the rat.

The late effects of heavy-ion irradiation on the spinal cord of the rat were investigated histologically and morphometrically. After a single exposure of each animal's lower thoracic and lumbar spinal cord to a carbon-ion beam, the animals were observed clinically for up to 69 weeks and their spinal cords were examined histologically after sacrifice. Paralysis of the hind limbs appeared from 16 to 20 weeks after irradiation with 20 Gy or more. The first histological change seen was vacuolization in the marginal white matter, which appeared 19 to 25 weeks after irradiation with more than 10 Gy. After irradiation with more than 15 Gy, bilateral destructive cavities occurred in the white matter, especially in the lateral tract. These histological changes were similar to those reported frequently for X irradiation. The mean cross-sectional area of the blood vessels in the irradiated spinal cord increased in a manner that was dependent on dose and was significantly larger 15 to 17 weeks after irradiation with 30 Gy. Reconstruction of small destructive lesions from serial sections consistently revealed dilated veins in the centers of these lesions. The effective dose that induces 50% incidence of hind-limb paralysis and destructive cavity formation (ED50) as determined using a curve-fitting method was 18.5 and 19.5 Gy, respectively, and the latent period was shorter than that for X irradiation.

Animals↗

PubMed1997

Heterogeneous distribution of early energy failure in experimental focal ischemia of the cat brain.

The distribution of succinate dehydrogenase (SDH) activity and the corresponding changes in specific gravity were studied in cats with experimental focal ischemia. Two hours of tandem occlusion of the middle cerebral artery (MCA) and the conunon carotid artery produced a scattered reduction of SDH activity and corresponding brain edema in the cortex. Recirculation ameliorated the SDH reduction and the scattered pattern disappeared, although the brain edema increased further. Four hours of focal ischemia resulted in diffuse reduction of SDH activity in the MCA-perfused area. The scattered area of SDH reduction after 2 hours of focal cerebral ischemia indicates that the ischemic core is multicentric in the early phase, and that these areas fuse together to form a well demarcated infarction, if the blood flow is not reestablished. A short period of cerebral ischemia produces multicentric small infarcts in the cortex, which resemble granular atrophy.

Animals↗

PubMed1997

Time course of tissue elasticity and fluidity in vasogenic brain edema.

We examined chronological changes in regional tissue elasticity (stiffness) and fluidity (1/viscosity) of the white matter during the development and resolution of vasogenic brain edema. Cryogenic injury was created in the cortex of cat brain, and the brain was prepared for measurement of regional tissue elasticity and fluidity. The results were then compared with the histology and tissue water content. Vasogenic edema developed in the white matter under the lesioned cortex (4-24 h) and was resolved by day 10. Regional tissue elasticity decreased significantly during the initial 24 h (45.3 +/- 32.5% of the control (mean +/- S.D.), and then increased to 158.6 +/- 32.3% of the control level at day 10. Regional tissue fluidity increased to 376.7 +/- 240.4% of the control level during the initial 24 h decreased to 77.7 +/- 17.9% of the control level at day 10. Histological examination of the white matter revealed widening of the inter-fiber space at 4-24 h after lesioning and astrocytosis at day 10. Thus vasogenic edema causes an increase of tissue fluidity with a decrease of tissue elasticity. Reactive astrocytosis after the resolution of edema causes an increase of tissue elasticity with mild decrease in tissue fluidity.

Animals↗

PubMed1997

Cystic ganglioneurocytoma outside the ventricular region.

Recently cases of ganglioneurocytoma and cerebral neurocytoma, very rare variants of central neurocytoma, have been reported. The former is characterized by differentiation toward ganglion cells and the latter by extraventricular origin in the cerebrum, but their existence as distinct clinicopathological entities, is controversial. We report an unusual case of neurocytoma, which arose extraventricularly from the frontal lobe, formed a large cystic lesion and showed ganglioid differentiation, in a 11-year-old girl. Following subtotal tumor resection, she showed a satisfactory clinical course and no evidence of recurrence. This is a very rare case of central neurocytoma-like tumor outside the ventricular system and also of ganglioneurocytoma. This case may provide some insight into the tumorigenesis and widen the clinicopathological concept of neurocytoma.

Brain Neoplasms↗

PubMed1997

Causality of parenchymal and vascular changes in rats with experimental thiamine deficiency encephalopathy.

The causality of vascular and parenchymal damage to the central nervous system (CNS) was examined in rats with thiamine deficiency. Male Sprague-Dawley rats were divided into two groups; one was given a thiamine-deficient diet (TDD) and injected intraperitoneally with 10 micrograms/100 g bodyweight pyrithiamine (PT) in order to analyze morphometrically the topographical and sequential relationship between vascular and parenchymal changes and vasodilatation, and the other was given a TDD and 50 micrograms/100 g bodyweight PT in order to determine hemorrhagic sites using serial sections. Histological examination showed that spongiotic change occurred selectively in the inferior colliculus (100%) from day 19, and thereafter in the thalamus (95%), mammillary body (50%) and nuclei olivaris and vestibularis of the pons (25%), with or without hemorrhage. Simultaneously, glycogen accumulation was also observed in these regions at a frequency similar to that of hemorrhage. Ultrastructurally, however, hydropic swelling of astrocytic and neuronal processes without glycogen accumulation was observed as early as day 9 in the inferior colliculus, at which time an increase of glial fibrillary acidic protein-positive processes was also recognized. The superior colliculus was completely spared. From day 22 vasodilatation of the inferior colliculus occurred, concomitantly with bodyweight loss and neurological symptoms. Twenty-two examined hemorrhages, which occurred in the thalamus and inferior colliculus, were distributed along the arterioles or capillaries on the arterial side. In conclusion, the morphological CNS changes caused by thiamine deficiency with administration of low-dose PT in rats begin as hydropic swelling of neuronal and astrocytic processes, followed by hemorrhage and, thereafter, by vasodilation. The predilection for hemorrhage on the arterial side without parenchymal changes suggests that petechial hemorrhage is not simply secondary to parenchymal changes, but is due to hemodynamic change resulting from thiamine deficiency-induced vascular dysfunction.

Animals↗

PubMed1996

The pyramidal cell layer of sector CA 1 shows the lowest hippocampal succinate dehydrogenase activity in normal and postischemic gerbils.

We examined regional differences in the activity of a mitochondrial respiratory enzyme, succinic dehydrogenase (SDH), in the hippocampi of normal and postischemic gerbils, using a quantitative imaging method. Gerbils (n = 21) without ischemia, and gerbils which had experienced 5 min of bilateral common carotid artery occlusion 12 h or 2 days previously, were sacrificed. Coronal sections of the brains were prepared for quantitative imaging of SDH activity and histological examination. In the control gerbils, SDH activity in the pyramidal cell layer of the CA 1 sector (Sommer's sector) was 106.3 +/- 10.3% (mean +/- SD; SDH activity as a percentage of the cerebellar SDH activity), which was lower than in the other subfields of the hippocampus. SDH activity in the oriens layer, stratum radiatum and lacunosum molecular layer of the CA 1 sector was lower than in the corresponding layers of the CA 2 and CA 3 sectors. After transient ischemia, SDH activity remained unchanged in the CA 1 sector. Histologically, selective neuronal necrosis was observed in the pyramidal cell layer of the CA 1 sector 2 days after ischemia. The observed low level of this mitochondrial respiratory enzyme in the pyramidal cell layer of the CA 1 sector should be taken into account as a possible trigger of the selective vulnerability of the region to ischemia.

Animals↗

PubMed1996

Metabolites of 5-fluorouracil, alpha-fluoro-beta-alanine and fluoroacetic acid, directly injure myelinated fibers in tissue culture.

The neurotoxicity of two 5-fluorouracil (5-FU) derivatives, tegafur (FT) and carmofur (HCFU), which selectively induce leukoencephalopathy involving the cerebral white matter in humans and vacuolation of myelinated fibers in dogs and cats, was examined in vitro. The common metabolites of these drugs, alpha-fluoro-beta-alanine (FBAL) and fluoroacetic acid (FA), were added to the medium of cultured murine cerebellar myelinated fibers. On day 1 of exposure to 7 microM FBAL and FA, which corresponds to their blood concentrations 2 h after oral administration of 10 mg.kg-1 HCFU to dogs that induced central nervous system vacuolation after 30 days, partial splits of the myelinic intraperiod line were observed by electron microscopy. On days 4-7, phase contrast microscopy revealed spindle-shaped swelling and granulation of myelin and electron microscopy demonstrated prominent dissociation of the myelinic intraperiod line with monolocular and multilocular vacuolation. More severe changes, such as myelin loss, were found in cultures exposed to a higher concentration (70 microM) of FBAL and FA, but no remarkable neuronal, astrocytic or oligodendrocytic changes occurred. Quantitative evaluation of myelin injury by electron microscopy revealed significant toxicity of FBAL and FA, at concentrations of 7 and 70 microM, on day 4. However, groups treated with 0.7 microM FBAL and FA, 5-FU (7 microM) and controls exposed to beta-alanine and acetic acid concentrations of 0.7, 7 and 70 microM showed no marked injury. We concluded that these anticancer drug metabolites injure myelin fibers directly, resulting in vacuolation due to myelin splitting and destruction.

Animals↗

PubMed1996

Proliferating cell nuclear antigen (PCNA) expressed in human leptomeninges.

Here we report on the presence of proliferating cell nuclear antigen (PCNA) in human leptomeninges from 35 normal subjects with ages ranging from 57 to 94 years. Strong immunoreactivity with PC10 (a monoclonal antibody to PCNA) was detected in the nuclei of meningothelial cells, smooth muscle cells of leptomeningeal vessels, and ependymal cells. An immunoblot of leptomeningeal homogenate with PC10 showed the presence of a single band at 35 KD, the expected molecular mass of PCNA. Ki-67, another marker for cell proliferation, was undetectable in human leptomeninges. These observations point to isolated PCNA expression in tissue in which cells are not actively proliferating.

Aged↗

PubMed1995

YM90K, an AMPA antagonist, has no neurotoxic effects on cerebrocortical neurons in rats.

The neuroprotective properties of glutamate receptor antagonists arise from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids. However, J. W. Olney et al. (1989, Science 224: 1360-1362) have reported that MK-801, an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, induced morphological damage in neurons in the cerebral cortex of rats. YM90K is a potent alpha-amino-3-hydroxy-5-methylisoxazole propionic acid receptor antagonist which has high neuroprotective efficacy against delayed neuronal injury. The purpose of this study was to investigate whether YM90K induces a vacuolar reaction in the cytoplasm of neurons similar to that seen after the administration of MK-801. All experiments were performed on female F344 rats. YM90K was administered by iv infusion for 3 h at the dose of 40 mg/kg/h. MK-801 was given by single sc injection at the dose of 1 mg/kg. All rats receiving MK-801 showed neuronal vacuolation. The affected neurons were recognized as medium-sized pyramidal-shaped neurons which were distributed between layers II and IV in the posterior cingulate and retrosplenial neocortices. Most of these vacuoles contained multiple small and round structures that appeared to be remnants of mitochondria. Other vacuoles were recognized as enlarged sER or those present within the bilaminar nuclear membrane. MK-801 also induced heat shock protein immunoreactivity in the same neurons. In contrast, no such pathomorphological changes could be detected in the YM90K-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Vascular changes in acute Wernicke's encephalopathy.

The nature and distribution of vascular changes in acute Wernicke's encephalopathy (WE) were analyzed in three autopsy cases. Lesions of the lateral vestibular nucleus of the medulla oblongata (three cases) and lateral ventricular wall (one case) were examined by reconstruction of 200 serial sections, and the capillary diameter in the tegmentum of the medulla oblongata was measured morphometrically in all cases. The vascular changes commonly found in and around the parenchymal lesions in all cases were: (1) dilatation and endothelial swelling of almost all vessels ranging from small arteries to veins, being especially severe with undulation in small arteries and arterioles, and (2) fibrinoid degeneration and hemorrhage involving selectively the arterioles and capillaries on the arterial side. These vascular changes in the medulla oblongata were essentially the same as those in the third ventricular wall, but differed in their severity. Capillary diameter in these cases was significantly larger than that in seven control cases. Such vascular changes, especially a dysoric change on the arterial side, could not be ascribed to secondary change following changes in the parenchyma, and were, therefore, considered to be a lesion essential to WE, as in the case of the parenchymal lesion.

Adolescent↗

PubMed1994

Is the swelling in brain edema isotropic or anisotropic?

A study was conducted to examine whether swelling of the brain due to vasogenic-type and cytotoxic-type edema is isotropic or anisotropic. Vasogenic edema was induced by cryogenic injury in cats, and coronal sections of the brain were examined at 4-5 h after injury. The swelling of the edematous white matter longitudinal to and transverse to the subcortical neuronal fibers was 2.3% and 91.1%, respectively. Ischemic edema was examined using cortical tissue specimens of cat brain subjected to either middle cerebral artery occlusion for 3 h or immersion in saline after decapitation for 3 h. The swelling parallel to the left-right axis, caudo-rostral axis and antero-posterior axis was 9.6%, 10.1% and 8.5%, respectively. Neuroglial cell swelling was prominent in the ischemic cortex. Thus swelling of the white matter in vasogenic-type edema was anisotropic, whereas that of gray matter in cytotoxic-type (ischemic) edema was isotropic. This observed difference in the biomechanical properties of brain tissue should be taken into account when the etiology of edema-mediated tissue injury, such as herniation, secondary bleeding or ischemia is investigated.

Animals↗

PubMed1994

Biomechanical characteristics of brain edema: the difference between vasogenic-type and cytotoxic-type edema.

Some of the basic biomechanical properties of edematous brain tissue have yet to be clarified. Therefore we measured regional tissue compliance and swelling isotropy/anisotropy in cat brain during development of vasogenic-type and cytotoxic-type edema. In vasogenic-type edema induced by cryogenic injury, the edematous white matter showed an increase of regional tissue compliance (indentation method), which paralleled the increase in the regional tissue water content (gravimetry). Swelling of the white matter due to edema was anisotropic, in which expansion transverse to the neuronal fibers caused by their dissociation was 91.1%, whereas longitudinal expansion was 2.3%. In cytotoxic-type edema induced by cerebral ischemia for 3 h, regional tissue compliance was decreased in the area suffering energy failure, which was visualized as an area of reduced succinic dehydrogenase activity. The ischemic gray matter showed isotropic swelling, and morphologically, prominent swelling of neuroglial cells. These marked differences in basic biomechanical properties between vasogenic-type and cytotoxic-type edema should be taken into account when analyzing the mechanism of edema-mediated tissue injury.

Animals↗

PubMed1994

Paraneoplastic encephalo-myelo-ganglionitis: cellular binding sites of the antineuronal antibody.

The cellular binding sites of an antineuronal antibody were characterized in an autopsy case of the paraneoplastic encephalo-myelo-ganglionitis. A 61 year-old woman developed a subacute sensorimotor polyneuropathy and, later, multiple involvement of cranial nerves, disturbance of consciousness, and generalized seizure. An autopsy revealed a small cell lung carcinoma and neuropathological changes that included disseminated encephalitis, spinal anterior horn lesions, severe loss of dorsal root ganglion neurons, and secondary degeneration and loss of the nerve fibers in the spinal posterior column and peripheral nerves. The serum IgG from the patient contained antineuronal antibody(s) including an antibody to 35- to 37-kDa neuronal antigens called anti-Hu as demonstrated in Western blot. In immunohistochemical studies, the serum IgG immunostained neurons of the brains, spinal cords, and dorsal root ganglia of humans or rats. Confocal laser-scanning microscopy revealed binding of the patient's IgG in the neuronal nuclei and cytoplasm, but not in the nucleoli. In immunoelectron microscopic studies, immunolabelling with the IgG was found diffusely in the karyoplasm, excluding nucleoli, and in the cytoplasmic matrix between the cisternae of the reticulums, Golgi apparatus, and mitochondria. Encephalo-myeloganglionitis is a clinicopathological entity frequently associated with the presence of neoplasm and antineuronal antibody, however, the role of the antibody in the pathogenesis remains to be elucidated.

Autoantibodies↗