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Biomedical subjects

R Okeda

Publications and source records attributed to R Okeda.

At least 91 records · Page 5Linked to original sources
PubMed1984

Neuropathologic study on chronic neurotoxicity of 5-fluorouracil and its masked compounds in dogs.

5-Fluorouracil (FU) and its masked compounds tegafur (FT) and carmofur (HCFU) were administered orally to Beagle dogs daily for 6 months, and their chronic neurotoxic effects were examined morphologically. In ten dogs that survived the 6-month treatment large vacuoles produced by splitting of the intraperiod line of myelin were observed in the fornix in the wall of the third ventricle. In severely affected dogs large vacuoles developed in the medial preoptic area, medial portion of the internal capsule, the area around the subthalamic nucleus and the mammillo-thalamic tract. Axons of myelinated fibers affected by vacuolation were generally well maintained, and destruction of myelin was not detected. Though proliferation of glia cells or abnormality of oligodendroglia was not detected, a lipid deposit covered by a single layer membrane was observed in the cell bodies and processes of astrocytes. No abnormality was detected by electron microscopy in the cerebrum, inferior colliculus, cerebellum, or pons. Of eight dogs that died during the treatment period, large vacuoles were observed in the fornix in the wall of the third ventricle of four dogs treated for more than 1 month, and large vacuoles were present in the inferior colliculus in two dogs of the FT group in the above four dogs. In the HCFU group, the interruption of treatment for 6 months resulted in alleviation or disappearance of the vacuolar lesions. The above findings suggest that the neurotoxicity of FU and its masked compounds FT and HCFU in long-term treatment produces changes morphologically identical with one another in respect to the site of their manifestation and nature of lesion, that their common degraded product alpha-fluoro-beta-alanine (FBAL) plays a crucial role in their neurotoxic actions, and that vacuolar lesions, to which myelin was more vulnerable than neurons, can develop where the toxic substance readily deposits and accumulates.

Animals↗
PubMed1984

Vascular changes of methotrexate-related disseminated necrotizing leukoencephalopathy.

We investigated cerebral lesions of methotrexate (MTX)-related disseminated necrotizing leukoencephalopathy (DNL) in two autopsy cases of leukemia by the reconstruction technique of the serial sections and thick sections (700-800 microns) stained with silver impregnation to detect the topographic relation between the vascular changes and parenchymal lesions. We revealed the vascular changes, such as fibrinoid degeneration, hyalinized thickening of the vascular wall, dilatation of lumen and stenosis due to swelling of the endothelial cells and exsudation in the wall, particularly prominent in venules and capillaries of venous side in the territory of the superficial medullary veins. There were no remarkable changes in the arteries, except for the moderate endothelial swelling of arteriolar capillaries. The parenchymal lesions were topographically associated with these vascular changes, and the small necrotic foci confluented each other and formed large irregular necrotic foci. We considered that the DNL may be ascribed to dyshoric damage of the veins and capillaries of the venous side and that the mechanism of vascular injury was probably due to the prolonged direct action of intrathecal MTX on the vessels.

Adult↗
PubMed1984

Progressive multifocal leukoencephalopathy associated with prolonged hemodialysis treatment.

The association of progressive multifocal leukoencephalopathy (PML) with prolonged hemodialysis treatment (PHT), not previously reported, was observed in a 56-year-old Japanese man who received PHT for 11 years. He suffered from recurrent bouts of fever and progressive neurological signs, such as irritability, speech disturbance, gait disturbance and dysphagia for seven months, and finally fell into a deep coma and died. Clinical signs and symptoms were highly suggestive of progressive dialysis encephalopathy. Necropsy revealed that the PML mainly involved the brainstem and cerebellar white matter. The aluminium content of the brain tissue was lower than that of controls. Possibly the virus causing PML is one of the causes of progressive dialysis encephalopathy, since clinically PML is not easily distinguished from progressive dialysis encephalopathy. It is essential to differentiate PML of viral etiology from progressive dialysis encephalopathy of unknown cause.

Brain↗
PubMed1984

A study of experimental cyanide encephalopathy in the acute phase--physiological and neuropathological correlation.

A study was performed to elucidate the significance of various physiological factors contributing to the pathogenesis of experimental cyanide encephalopathy, such as the systemic arterial blood pressure, venous pressure, common carotid blood flow and local blood flow of the cerebral grey and white matters, and blood gas including pH. The histology and topography of the brain damage was also analysed. Twenty-one cats were divided into four groups. The animals in groups 1, 2 and 3 were subjected to continuous infusion of 0.2% sodium cyanide solution and to the ensuing hypotension below 100 mm Hg by administering a ganglion-blocking drug and by respiratory arrest. Severe damage developed in the deep cerebral white matter, corpus callosum, pallidum and substantia nigra, but the damage of the cerebral cortex and hippocampus was not remarkable. The animals in group 4 that were subjected to cyanide infusion without significant hypotension (above 100 mm Hg), but to the same degree of acidosis as that of the other groups, had similar morphological changes, but to a lesser degree. On the basis of our physiological and morphological findings, we speculated that the pathophysiological factors of tissue hypoxia and subsequent hypotension operated in cyanide leucoencephalopathy. The topographic selectivity seemed to be related to the characteristic cerebral vascular system, and the severity of the white matter lesions was related to the intensity of both hypoxia and hypotension during cyanide infusion, but not to the extent of acidosis, total dose of cyanide or duration of its infusion per se.

Acute Disease↗
PubMed1984

An autopsy case of acute porphyria with a decrease of both uroporphyrinogen I synthetase and ferrochelatase activities.

An autopsy case of a 37-year-old woman with acute porphyria is reported. The patient began to complain of severe menstrual pains, and later developed serious peripheral neuropathy and various autonomic nervous symptoms. The autopsy revealed a marked loss and degeneration of axons and myelin sheaths in the peripheral nervous system (PNS), and prominent central chromatolysis of the spinal anterior horn cells. The predominant process of the peripheral neuropathy appeared to be axonal degeneration. Biochemical analysis showed a marked increase of delta-aminolevulinic acid (ALA), porphobilinogen, uroporphyrin, and coproporphyrin in the urine, and an increase of coproporphyrin and protoporphyrin in the stools and blood. In the analysis of the enzymatic activities of the liver and bone narrow, the activity of ALA synthetase (ALA-S) was markedly increased, and the activities of both uroporphyrinogen I synthetase (URO-S) and ferrochelatase were decreased. It was characteristic in this case that the enzymatic abnormalities found in both acute intermittent porphyria (AIP) and variegate porphyria (VP) coexisted. Biochemical analysis of the sciatic nerve showed an increase of ALA-S activity and a decrease of both URO-S and ALA dehydrase activities. This was the first report that indicated the presence of abnormal activities of the heme biosynthetic enzymes in the peripheral nerves of porphyric patients. The possibility was discussed that these enzymatic abnormalities of the heme biosynthesis in the peripheral nerve itself might be strongly related to the pathogenesis of the porphyric neuropathy.

Adult↗
PubMed1984

Pineocytoma. Observation of an autopsy case by electron microscopy and cell markers.

An autopsy case of a 69-year-old female with pineocytoma was reported. The tumor showed neuronal differentiations, which were confirmed not only by light microscopy and electron microscopy, but also by a cell marker of neuron-specific enolase. In addition, existence of astrocytes in the tumor which distributed sparsely was ascertained by electron microscopy and cell markers such as S-100 protein and glial fibrillary acidic protein.

Aged↗
PubMed1983

Hemimegalencephaly with hemihypertrophy (Klippel-Trénaunay-Weber syndrome).

A 17-year-old Japanese girl had right hemihypertrophy, vascular nevus of the right side of the body, right hemimegalencephaly, multiple haemangiomatosis, varicosis and chronic proliferative glomerulonephritis. The hypertrophied side of the cerebrum showed no malformations. Quantitative studies showed no significant differences between the two cerebral hemispheres in size, form, density or DNA content of nerve and glial cells. The hemimegalencephaly seemed to be due to an increase in the absolute number of nerve and glial cells in the ipsilateral cerebral hemisphere. Eight cases of hemihypertrophy with hemimegalencephaly have been reported to date, in all of them hemihypertrophy and hemimegalencephaly were on the same side. This condition seems to be due to unilateral overproduction of neuroblasts and glioblasts or hindrance of the normal loss of excess neurons, which may be induced by hemihypertrophy of the mesenchyme surrounding the CNS.

Adolescent↗
PubMed1983

An experimental study of the pathogenesis of the selective lesion of the globus pallidus in acute carbon monoxide poisoning in cats. With special reference to the chronologic change in the cerebral local blood flow.

Twenty-eight mature cats were exposed to 0.3% carbon monoxide (CO) gas for 90-193 min using artificial ventilation. The systemic blood pressure (BP), venous pressure (VP), blood flow of the left common carotid artery (CF), and blood gas were monitored. The local blood flow (LBF) of the globus pallidus, putamen, or claustrum was measured by the hydrogen clearance method. Pallidal lesions were found histologically in 14 cats. The period of CO inhalation and the time thereafter were divided into the following four stages in the animals with pallidal lesions. Stage 1: Initial phase with rapid increase in the CF and LBF, and rapid decrease in the BP. Stage 2: Middle phase with slow decrease in the BP, CF, and LBF. Stage 3: Terminal phase with rapid decrease in the BP, CF, and LBF. Stage 4: Recovery phase. The changes in stage 3 were not so prominent in the animals without pallidal lesions. The LBF of the globus pallidus of the animals with lesions decreased to 67.3 +/- 20.7% of the initial value at the terminal stage of CO inhalation, while it was 188 +/- 46.7% in those without lesions. The difference was statistically significant (P less than 0.01). The LBF of the putamen or claustrum in the animals with lesions in the globus pallidus was 140 +/- 24.6% at this stage, and it was significantly higher than that of the globus pallidus (P less than 0.01). Other factors, such as CO inhalation time, degree of acidosis, and terminal CO-Hb concentration, did not correlate with the occurrence of the pallidal lesion.

Animals↗
PubMed1982

Comparative study on pathogenesis of selective cerebral lesions in carbon monoxide poisoning and nitrogen hypoxia in cats.

Since in a previous study hypoxia and subsequent hypotension were considered to be essential for the pathogenesis of carbon monoxide encephalopathy (CO-encephalopathy), experiments were conducted to see whether a combination of nitrogen hypoxia and subsequent systemic hypotension of similar degree and duration as in the previous experimental CO poisoning could induce the same lesion in the CNS of cats. The partial pressure of blood oxygen was reduced to less then 26 mm Hg by increasing the concentration of nitrogen in N2/O2 gas to be inhaled in 1.5h and then the aortic blood pressure (BP) was reduced to 60-80 mm Hg by blood depletion and ganglion-blockage for 1h. In 11 of the 15 cats, lesions were produced in the CNS which were similar by light and electron microscopy to those in CO-encephalopathy. In control groups which were treated by hypoxemia only, hypotension only or a combination CO2-gas inhalation and hypotension without hypoxemia, such lesions were not found in the cerebral white matter. Considering the pathogenesis of lesions in the cerebral white matter in both nitrogen hypoxia and CO-poisoning, two factors i.e., hypoxemia and subsequent systemic hypotension, are common and essential. Further, the enormous vasodilatation in the cerebral white matter induced by hypoxemia and subsequent drop in BP seem to cause a more severe circulatory disturbance in the cerebral white matter than in the cortex.

Animals↗
PubMed1982

Electron microscopic observations of experimental carbon monoxide encephalopathy in the acute phase.

The cerebral and cerebellar lesions of the cats that were exposed to 0.3% carbon monoxide gas under artificial respiration were examined by an electron microscope at different intervals. During the first few days, the most outstanding features were segmental empty axonal swelling, dilatation of the extracellular space, swelling and necrosis of astrocytes and oligodendroglias, and lamellar separation of the myelin sheath predominantly in the deep cerebral white matter. These changes subsided within one week. Instead, collapsed myelin increased in number and phagocytosis of disintegrated myelin was occasionally observed. Astrocytes and oligodendroglias became prominent in size and number. Changes suggestive of selective damage of myelin or oligodendroglia was not encountered. We proposed that CO-followed by Wallerian degeneration. The pathogenesis of CO-encephalopathy was also discussed.

Animals↗
PubMed1982

[An autopsy case of Parkinson's disease associated clinically with dementia terminating in akinetic mutism and pathologically with multiple Lewy's Bodies in the cerebral cortex].

An autopsy case of a 50 year-old male with Parkinson's disease associated with multiple Lewy bodies in the cerebral cortex was reported. His clinical symptoms began at the age of 26 with the speech and actions indicative of a persecution complex accompanied by irritability and were followed by progressive dementia from the age of 37 and Parkinsonism since the age of 41. He was in a state of akinetic mutism thereafter till his death at the age of 50. Autopsy disclosed in addition to the typical findings of Parkinson's disease in the brain stem multiple intracytoplasmic Lewy bodies in medium-sized neurons of the fifth and sixth layers of the cerebral cortex. They were atypical in the sense that they did not have any haloes. They were especially numerous in the cingulate gyrus. In addition, findings of non-specific neuronal degeneration were obtained in the cerebral cortex such as cellular atrophy with massive deposition of lipofuscin pigments, central chromatolysis, cell loss and cellular gliosis in the third, fifth and sixth layers. These neuronal findings were also prominent in the cingulate gyrus. Such senile changes as senile plaques or granulo-vacuolar degeneration were not found, although there were a few foci of neurofibrillary degeneration in the hippocampal gyrus. Histochemically and electron microscopically, no difference was observed in the constituents of Lewy bodies between the brain stem and the cerebral cortex. Such autopsy findings and a review of the literature indicate that the dementia in this case may be related not only to the presence of Lewy bodies but also to the above-described, non-specific neuronal degeneration in the bilateral cingulate gyri and surrounding frontal gyri. The standpoint of regarding a Parkinson's disease with multiple Lewy bodies in the cerebral cortex as an independent disease entity was criticized.

Akinetic Mutism↗
PubMed1981

Direct effects of carbon monoxide on cardiac function.

The direct effects of carbon monoxide (CO) on cardiac function were investigated in hemoglobin-free living rabbits treated with perfluorochemical blood substitutes. After exchange transfusion with a perfluorochemical emulsion, the erythrocyte count was below 10 X 10(4)/mm3 in each animal. Gas mixtures of oxygen with 5%, 10%, and 20% of CO or nitrogen were administered via a respirator. The results showed that the cardiac effects of CO and nitrogen were significantly different as regards changes in arterial pressure, pulse pressure, heart rate, and the product of heart rate and systolic arterial pressure in spite of the same oxygen tension in the inhaled gases. It was concluded that there was a direct effect of CO not mediated by hemoglobin.

Animals↗