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Biomedical subjects

R Okeda

Publications and source records attributed to R Okeda.

At least 73 records · Page 4Linked to original sources
PubMed1989

Experimental study on subacute neurotoxicity of methotrexate in cats.

An experimental study on the pathogenesis of methotrexate (MTX)-related neurotoxicity including disseminated necrotizing leukoencephalopathy (DNL) was conducted in cats. MTX was administered to the cerebrospinal fluid (CSF) of adult cats using either an intracisternal intermittent instillation (ICI) model or an intraventricular continuous instillation (IVC) model. Furthermore, the synergistic effects of CSF-flow disturbance with kaolin-induced hydrocephalus, and 60Co irradiation were morphologically examined in these models. None of the animals from either the ICI and IVC groups showed DNL, but all animals showed segmental axonal degeneration, suggesting that MTX had a direct toxic effect on the axon. In the ICI groups, no apparent synergistic effect of CSF-flow disturbance and radiation was noted on this axonal change. In the IVC groups, CSF-flow disturbance augmented the degree of the axonal injury. Axonal degeneration and fibrin exudation in the walls of small blood vessels occurred in one animal of the IVC groups with CSF-flow disturbance, suggesting that a toxic effect of MTX on blood vessels is another mechanism of MTX-induced neurotoxicity.

Animals↗
PubMed1989

Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia.

The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia.

Animals↗
PubMed1989

Hydrodynamics of arterial branching--the effect of arterial branching on distal blood supply.

A study was conducted to investigate the hydrodynamics of branching flow in relation to the blood supply to the basal part of the brain. A series of measurements of the branching loss-coefficients under laminar steady flow were conducted using model branches with various geometries, and the effect of branching on blood supply to distal areas was described using a lumped-parameter model of the vascular structure. It was revealed that in the blood circulation, branching loss is important where a small artery divides off with a large branching angle from a large trunk. It was also indicated that the effect of such branching on the distal blood supply might become more significant when the peripheral resistance is reduced, thereby increasing the blood velocity in the trunk.

Animals↗
PubMed1988

Blood-brain barrier disruption and exacerbation of ischemic brain edema after restoration of blood flow in experimental focal cerebral ischemia.

The mechanism of exacerbation of ischemic brain edema after blood flow restoration was studied in 20 cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow was measured by the hydrogen clearance method, and the left middle cerebral artery (MCA) was occluded for 6 h in group A, and for 3 h with subsequent 3 h recirculation in group B. Severity of brain edema was assessed by specific gravity measurement of tissue samples taken from coronal brain sections at the MCA area, while severity of blood-brain barrier (BBB) disruption was determined by measuring the amount of extravasated serum albumin by using [125I]albumin and tissue-uptake method in the same samples as those used for gravimetry. Structural and ultrastructural change was correlated with the severity of ischemic brain edema and BBB disruption. The results obtained showed that: (i) ischemic brain edema observed in group A was not associated with BBB opening to serum proteins; (ii) ischemic edema in group B was exacerbated significantly after recirculation in correlation with serum protein extravasation in most of the post-ischemic area; (iii) in the severely edematous area, serum protein extravasation reached a plateau and morphological examination at this type of area revealed cell membrane disruption especially of astrocytes, with leakage of intracellular substances. Our study indicated that the increase of extracellular osmotic pressure due to leakage of serum proteins via the disrupted BBB and of intracellular substances via the ischemically injured cell membrane into the extracellular space is the mechanism responsible for edema fluid accumulation in exacerbated ischemic brain edema.

Animals↗
PubMed1988

Subacute neurotoxicity of 5-fluorouracil and its derivative, carmofur, in cats.

The subacute neurotoxicity of 5-fluorouracil (FU) and its derivative, carmofur (HCFU), in cats was morphologically examined; both these drugs were orally administered once daily for a maximum of three months. The dosis of FU and HCFU was 2 mg/kg/day and 10 mg/kg/day, respectively. Both FU and HCFU induced two sorts of changes in the brain, i.e., vacuolation and softening-like change. The former was distributed in the white matter of the cerebrum and cerebellum and in areas of the gray matter such as the tectum and tegmentum of the brain stem, while the latter was distributed exclusively in the gray matter of the tectum and tegmentum of the brain stem. The tectum, especially the inferior colliculus, was most frequently affected by both types of change. Ultrastructurally, vacuolation was found to be due to lamellar splitting or separation between the axon and innermost myelin layer. These findings were compared with those in dogs and as the etiopathogenesis vacuolation due to direct toxic effect of FU or its metabolites to myelin and softening-like change due to local circulatory disturbance caused by vacuolation were proposed.

Animals↗
PubMed1988

Encephalomyeloneuritis with mediastinal germ cell tumor. A paraneoplastic condition?

An unusual case of encephalomyeloneuritis associated with germ cell tumor with mature and immature teratoma arising int he mediastinum is presented. There was an unusually long interval from the onset of neurologic symptoms to the development of malignancy. The histopathology, characterized by limbic encephalitis, brain stem encephalitis, cortical cerebellar degeneration and myeloneuritis, was similar to that of paraneoplastic encephalomyeloneuritis previously described in the literature. Virological and immunological studies failed to demonstrate any causative agents or autoantibodies reacting with brain tissue. The causal relationship between the malignant neoplasm and encephalomyeloneuritis thus seems to be very complex.

Adult↗
PubMed1987

Regional cerebral blood flow of acute carbon monoxide poisoning in cats.

The mechanism of selective vulnerability of the cerebral white matter and pallidum in acute carbon monoxide (CO) poisoning was experimentally investigated by measuring regional cerebral blood flow (rCBF) with the iodo-[14C]antipyrine method. A CO group consisting of five cats was exposed to 0.2%-0.3% CO gas and the rCBF was measured when moderate systemic hypotension (70-80 mm Hg) occurred; because systemic hypotension of this level during exposing to 0.2%-0.3% CO gas induces typical cerebral lesions of acute CO poisoning in almost all cats [Okeda et al. Acta Neuropathol (Berl) 54:1-10 (1981)]. Controls were a hypotension group of three cats with moderate systemic hypotension induced for 1 h without CO exposure, and a control group of five cats which inhaled only air for 2 h. The rCBF of each structure in the CO and hypotension groups was evaluated as a percentage of that of the control group. The rCBF of the CO group exhibited a wide range (68%-127%) according to the structures examined, and the mean (94.6%) was large compared with that (range: 53%-82%, mean: 67.4%) of the hypotension group. In the CO group, the examined brain structures where divided in two groups according to the rCBF values; low-value structures and high-value structures. There was significant (P less than 0.05) difference between rCBFs of both the structure groups. The cerebral white matter and pallidum belonged to low-value structures, and these rCBFs did not show any significant difference from those of other structures in this structure group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

[Melanosis of choroid plexus papilloma of the lateral ventricle: a case report].

A case of pigmented, well differentiated, choroid plexus papilloma is reported. A 45-year-old man came to our hospital complaining of attacks of vertigo and nausea. Skull X-ray films and CT scan demonstrated a calcified tumor in the left middle fossa. Tumor removal was done, and it was found that the tumor occupied the inferior horn of the left lateral ventricle. Histological examination revealed well differentiated choroid plexus papilloma containing various shaped pigment granules in the cytoplasm. The pigment granules in the tumor cells were stained black by Fontana-Masson method for melanin. The stain was negative in a section subjected to oxidative bleach. Granules were PAS-positive and autofluorescence. Therefore, the pigment granules had properties of both melanin and lipofuscin. In the electron microscopic study the ultrastructural appearance of the pigment was similar to that of neuromelanin, but not to that of pre-melanosome of neural crest origin. The pigment in this case seemed to be formed by "melanization" of lipofuscin as Barden's theory of pseudo-peroxidation. There are several case reports of pigmented choroid plexus carcinoma. However, no case of pigmented, well differentiated choroid plexus papilloma has, so far, been reported.

Cerebral Ventricle Neoplasms↗
PubMed1986

Chronic manganese poisoning: a neuropathological study with determination of manganese distribution in the brain.

An autopsy case of a 52-year-old man suffering from chronic manganese poisoning (CMP) is reported with determination of the manganese distribution in the brain. The patient had been working in a manganese ore crushing plant since 1965. In 1967 he began to complain of difficulties in walking and diminished libido. Later, he developed various neuropsychiatric symptoms including euphoria, emotional incontinence, masked face, monotonous speech, "cock-walk", increased muscle tone, weakness of upper and lower extremities, tremor of the eye lids, and exaggeration of knee jerks. The major neuropathological change was degeneration of the basal ganglia, in which the pallidum was severely affected. The pallidum disclosed a loss and degeneration of nerve cells, which was especially marked in the medial segment, a prominent decrease of myelinated fibers, and moderate astrocytic proliferation. The substantia nigra was intact. Distribution of manganese in the brain of the present case of CMP was determined using flameless atomic absorption spectrometry and compared with control cases and also a case of Parkinson's disease (PD). There was no significant difference between the control cases and the case of PD in average concentration of manganese and its distribution in the brain. The present case of CMP showed no elevation in average concentration of manganese in the brain. However, there were some changes in its distribution. Thus, the continuance of neurological disorders in CMP is not linked to an elevated manganese concentration itself in the brain. CMP appears to be different from PD in neuropathology and manganese behavior in brain.

Aged↗
PubMed1986

Experimental study on pathogenesis of the fetal brain damage by acute carbon monoxide intoxication of the pregnant mother.

The pathogenesis of fetal brain damage caused by acute maternal carbon monoxide (CO) intoxication was experimentally investigated in cats; 11 pregnant cats in various gestational stages were exposed to 0.2-0.3% CO/air gas for 76-150 min; thereafter, 29 live and stillborn neonates and 14 fetuses removed by cesarean section were observed pathologically. In the full-term or late-gestational-stage fetuses and neonates, the most vulnerable areas were the cerebral white matter and brain stem, followed by the basal ganglia and thalamus, and then the cerebral cortex. No changes were found in the cerebellum. From the distribution and nature of the brain changes, a hypoxic-ischemic mechanism was proposed as the pathogenesis of fetal brain damage. In the fetuses or neonates in middle and early gestational stages, the frequency and severity of the brain changes were generally lower than in those in the late gestational stage, and the cerebral white matter and basal ganglia were most often involved, but the thalamus, brain stem and the cerebral cortex were spared. The severity and extent of the brain changes were not the same among all littermates, but varied from normal to severely damaged animals. Among the maternal physiological factors measured during the CO exposure, only the severity of acidosis was correlated with the grade of fetal brain damage.

Animals↗
PubMed1986

Distribution of demyelinating lesions in pontine and extrapontine myelinolysis--three autopsy cases including one case devoid of central pontine myelinolysis.

Three autopsy cases of pontine and extrapontine myelinolysis are reported; one, a malignant lymphoma in a man of 66 years, the other an alcoholic liver cirrhosis in a man of 54 years, and an esophageal cancer in a woman of 68 years who presented only with extrapontine myelinolysis, but lacked central pontine myelinolysis (CPM). The extrapontine lesions in these three cases revealed a characteristic and common localization; they occurred mostly in the bundles of myelinated fibers in the gray matter, such as in the pons, basal ganglia, and thalamus; and in the white matter surrounded by massive gray matter, such as the deeper layers of the cortex and subjacent white matter of the crowns and sides of the cerebral gyri, the white matter of the cerebellar folia and internal, external, and extreme capsules. Therefore, the third patient was classified as a subtype of pontine and extrapontine myelinolysis, which may be called the "extrapontine form" because of absence of CPM. Moreover, bilateral demyelination of the mamillary body was found in all cases, and laminar cortical astrocytosis and necrosis similar to Morel's cortical laminar sclerosis in two of them. From the clinical and pathologic findings, the significance of the changed osmolarity of the blood as a cause and the importance of some specificity of the tissue architecture in the pathogenesis are discussed.

Aged↗
PubMed1986

Cornelia de Lange syndrome with intracranial germinoma.

An autopsy case of Cornelia de Lange syndrome with intracranial germinoma is reported. Clinically, the patient was diagnosed as having this syndrome at one year of age, she was found to be suffering from diabetes insipidus at 18 years of age and soon she had an accidental death. The autopsy disclosed that the tumor grew from the hypothalamus to the optic nerve and the posterior lobe of the hypophysis. Microscopically, this tumor was a germinoma with a "two cell pattern". On the other hand, examination by peroxidase-antiperoxidase complex (PAP) method of the anterior lobe of the hypophysis demonstrated that thyroid-stimulating hormone (TSH) and follicle-stimulating hormone (FSH) producing cells had decreased.

Adolescent↗
PubMed1986

Discrepancies among CT, histological, and blood-brain barrier findings in early cerebral ischemia.

The development of ischemic edema and blood-brain barrier (BBB) disruption during the 1st day of experimental cerebral infarction induced by transorbital occlusion of the middle cerebral artery (MCA) in cats was evaluated by computerized tomography (CT) scanning and compared to gravimetric and pathological studies. Regional cerebral blood flow was measured using the hydrogen clearance technique or stable xenon-enhanced CT scanning. Edema was observed gravimetrically and microscopically as early as 1 hour after the onset of ischemia in the cortex and at 3 hours or later in both the cortex and white matter. However, a significant decrease of Hounsfield numbers on the CT scans was not detectable at 1 or 3 hours and was scarcely visible at 9 hours after occlusion. Disruption of the BBB was detected by leakage of Evans blue dye at 3 hours after the occlusion in two of six animals and at 9 hours in five of five animals. However, CT scanning after infusion of contrast material showed no significant increase in Hounsfield number even 24 hours after MCA occlusion. These discrepancies should be emphasized when the dynamics of ischemic edema and BBB disruption are evaluated for clinical therapy by CT scanning.

Animals↗
PubMed1986

Cerebral thrombosis at altitude: its pathogenesis and the problems of prevention and treatment.

In analyzing cerebral thrombosis at altitude--own case and in the literature--we anatomically confirmed that cerebral thrombi in mountain sickness were all of venous origin. All climbers went higher than 5,000 m and most stayed in that altitude longer than 3 weeks. Hemoconcentration was confirmed in two cases, including our own patient. It was suspected that hemoconcentration resulting from secondary polycythemia and dehydration at altitude, as well as cerebral circulatory disturbance produced by high-altitude cerebral edema, played a major role in the development of cerebral thrombosis. The problems of prevention and treatment of cerebral thrombosis at altitude are discussed.

Adult↗
PubMed1985

Neoplastic angioendotheliosis. Immunohistochemical and electron microscopic findings in three cases.

Three cases of neoplastic angioendotheliosis (NAE) presenting with central nervous system (CNS) disease but no skin lesions are described. The histogenesis of the neoplastic cells is discussed. Microscopic examination showed accumulation of neoplastic cells in the vascular system throughout the body and their extravascular proliferation in several organs. Electron microscopic and immunohistochemical studies revealed the presence of Weibel-Palade bodies and factor VIII-related antigen in intravascular and extravascular neoplastic cells in two of the three cases. In the first case the neoplastic cells did not have any T-cell markers. However, in one case no specific markers were found in the neoplastic cells by electron microscopic, enzyme histochemical, or immunohistochemical examination. These findings, although supporting the endothelial origin of the neoplastic cells, indicate the need for further consideration of whether NAE is actually a single disease entity or several different diseases.

Aged↗
PubMed1985

Cortical cerebellar degeneration with testicular neoplasm.

Cortical cerebellar degeneration was found in a 28-year-old man with testicular neoplasm. The patient, who had undergone a left orchidectomy for the testicular tumor, developed progressive cerebellar symptoms with mental changes 7 months later. The autopsy revealed the spread of a malignant germ cell tumor of the testis, and cortical cerebellar degeneration in the central nervous system (CNS) which was characterized by almost complete loss of Purkinje cells and degeneration of the both dentate nuclei and superior cerebellar peduncles. The present case is the first of cortical cerebellar degeneration combined with testicular neoplasms.

Adult↗
PubMed1985

Direct effect of carbon monoxide on hexobarbital metabolism in the isolated perfused liver in the absence of hemoglobin.

The interaction of carbon monoxide (CO) with cytochrome P-450 associated with hexobarbital metabolism was observed in hemoglobin-free perfused rat liver by using a scanning reflectance spectrophotometer. The evidence obtained showed that CO bound to the substrate complexed cytochrome P-450 and, at a CO/O2 ratio of over 0.1 in the perfusate, inhibited the hexobarbital metabolism estimated from the hexobarbital uptake, and oxygen consumption. Although the oxygen supply to the liver cell was one of the major limiting factors during CO hypoxia, CO binding to cytochrome P-450 significantly enhanced the suppression of hexobarbital oxidation caused by hypoxic hypoxia.

Animals↗