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Biomedical subjects

R Okeda

Publications and source records attributed to R Okeda.

At least 55 records · Page 3Linked to original sources

Evidence for an origin of ethyl-nitrosourea-induced rat central nervous system tumors from pluripotent germinal neuroepithelium.

Brain tumors induced by transplacental application of ethyl-nitrosourea (ENU) in F344 rats were immunohistochemically demonstrated to consist of undifferentiated cells, astriocyte-like cells, oligodendroglia-like cells, and two distinct types of vimentin-expressing cell groupings termed as perivascular small cell nests (PSCNs) and large cell nests (LCNs). Co-distribution of vimentin and glial fibrillary acidic protein (GFAP) was sparsely observed in the astrocyte-like cells, which suggested an immature glial phenotype. PCSNs contained cells expressing GFAP, neuron-specific enolase (NSE), beta-tubulin isotype III, and low-affinity nerve growth factor receptors (LNGFRs). LCNs contained cells showing a neuronal phenotype with expression of low- and middle-molecular mass neurofilament proteins (NF-L and -M) as well as NSE, beta-tubulin isotype III and LNGFR. Double-labelling immunohistochemistry revealed the NF-L-expression in LNGFR-positive LCN-forming cells. Oligodendroglia-like cells and their intercellular neuropil-like structures expressed beta-tubulin isotype III, synaptophysin and NSE, in addition to the expressions of vimentin and GFAP. Electron microscopically, synapse-like structures were formed between these oligodendroglia-like cells and their dendritic processes. Topographically, bidirectional cell transitions from PSCNs to astrocytes and LCNs were indicated. The present study strongly suggests that so-called ENU-induced "gliomas" originate from pluripotent germinal neuroepithelium. Furthermore, LNGFR expression may be responsible for acquisition of neuronal phenotype in these tumors.

Animals↗

Motor neuron disease with dementia and ophthalmoplegia. A clinical and pathological study.

Ophthalmoplegia and dementia are not usually observed in patients with amyotrophic lateral sclerosis. We report the case of a 60-year-old female with ophthalmoplegia and frontal-type dementia which appeared at an early stage of her illness that presented with dysarthria and weakness in the upper extremities. Notable autopsy findings in the central nervous system were, in addition to the degeneration of upper and lower motor neurons, moderate neuronal loss and spongy degeneration in layer II of the frontal cortex with prominent astrocytosis, and moderate neuronal loss with astrocytosis in both the substantia nigra and the red nucleus. Central chromatolysis of a few neurons in the oculomotor nucleus was seen. This case is considered to be a new subtype of motor neuron disease.

Atrophy↗

Selective distribution of medial thickening in the renal vessels in experimental hypertension.

Direct effects, especially the distribution of medial thickening due to chronic hypertension on the renal arterial tree, were examined pathologically and morphometrically in cats with one-kidney DOCA-salt hypertension. Twenty-one adult male cats were divided into three groups: (i) an experimental group of one-kidney DOCA-salt hypertension (12 cats): (ii) a uninephrectomized group without administration of DOCA and salt (four cats); and (iii) a group without uninephrectomy and administration of DOCA and salt (five cats). The duration of hypertension varied from 3 weeks to 4 months and the aortic blood pressure was monitored every 5 min. The increase of mean blood pressure (MBP) of the experimental group was 15-44 mmHg. A significant medial thickening of the right renal arterial tree was evaluated by a comparison of the right and left regression lines of each case between the midwall radius (R) and medial thickness (D) of arteries in a distended state. The evaluation was made separately for arteries with R values above or below 40 microns, because a regression line between R and D showed a maximum bend at a level of R from 30 to 40 microns. The arteries of the right kidney with a diameter less than 40 microns, corresponding to the interlobular arteries and afferent arterioles, showed significant medial thickening in six cases. Medial thickening was absent in other cats of the experimental group and cats of a control group given uninephrectomy alone. Increase of MBP during the hypertensive phase of these six cases was above 34.6 mmHG and all values of other cats without medial thickening were below this level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neuropathology of cerebral ischemia and hypoxia: recent advances in experimental studies on its pathogenesis.

Cerebral hypoxia and ischemia are two of the most common disorders of the central nervous system. The pathomechanism has been a focus of interest in neuroscience for many years not only because of the clinical significance but also because of the peculiar distribution of the lesion (selective vulnerability) depending on the type of injury. This article reviews recent advances in the study of hypoxia-induced tissue injury of the central nervous system.

Anemia↗

Localization of HSP90 in rat brain.

1. In rats, HSP90 (90-kDa heat shock protein) was abundant in the brain compared with the liver and kidney. Immunohistochemical studies showed the presence of HSP90 in almost all neurons in the brain. 2. On immunoblotting using an anti-HSP90 antibody, HSP90 was present in a lower amount in the medulla oblongata and spinal cord. 3. In the pituitary gland, some of superficial cells of the anterior lobe adjacent to the middle lobe was specifically stained with anti-HSP90 antibody.

Animals↗

An experimental model for anaplastic astrocytomas and glioblastoma using adult F344 rats and N-methyl-N-nitrosourea.

An experimental model for induction of gliomas corresponding to human anaplastic astrocytomas and glioblastomas is reported. Eleven week old F344 and ACI rats were given 100 or 200 p.p.m. N-methyl-N-nitrosourea (MNU) solution as their drinking water for 42 weeks. Gliomas were induced at very high incidences (82.5-92.5%) in each group. Induced gliomas showed apparent evidence of morphologic malignancy by an analysis based on diagnostic criteria of human astrocytomas. All of the gliomas from the killed animals were classified histologically into subtypes according to the classification scheme used in the diagnosis of human gliomas. The majority of macrotumors more than 1 mm in diameter in both strains were diagnosed as anaplastic astrocytomas and glioblastomas. Immunohistochemically, tumor cells in these tumors were almost negative for glial fibrillary acidic protein, while ultrastructurally neoplastic astrocytes contained glial filaments. A strain difference was observed in the ratio of histological subtypes of macrotumors. In F344 rats, astrocytic tumors diagnosed as anaplastic astrocytomas and glioblastomas of an astrocytic type formed the majority, whereas glioblastomas of mixed oligo-astrocytic type predominated in ACI rats. The results indicate that MNU-administration to adult F344 rats may provide a suitable experimental model for gliomas which occur in adult humans.

Animals↗

Pathological effects of maternal hypoglycemia on fetal development in cats.

The pathogenesis of fetal brain damage caused by acute maternal hypoglycemia was investigated experimentally in cats: profound hypoglycemia (blood glucose concentration: less than 30 mg/dl) was induced in 12 pregnant cats at various stages of gestation by intravenous bolus injections of insulin. Maximal hypoglycemia was attained within 2-3 h, although the grade and duration in individual cats varied. The EEGs of all of seven maternal cats examined showed an increased frequency of slow high-voltage waves as hypoglycemia progressed, eventually becoming flat in 3 for a maximum period of 20 min. Some fetuses showed severe neuropathological changes, such as infarction or intrauterine death. Subventricular softening, cortical hemorrhage and ischemic neuronal changes also occurred, being distributed symmetrically in the parasagittal areas of the cerebrum, basal ganglia, thalamus and tegmentum of the brainstem. In general, these pathological changes were more marked in fetuses and neonates than in the maternal cats, in which only ischemic neuronal changes were present, and may have been due to fetal systemic hypotension and cerebral ischemia induced by hypoglycemia. In maternal cats, the distribution of neurons showing ischemic changes was widest in the cerebral cortex, and some were also present in the dentate gyri of the hippocampus. Moreover, ultrastructural examination of the ischemic neurons in maternal cats, unlike those of the fetuses, showed no mitochondrial swelling. Therefore, the distribution and ultrastructural nature of the ischemic neurons found in the maternal cats were considered to be characteristic of hypoglycemia, as proposed by Agardh et al. (1980).

Animals↗

[An autopsy case of untreated systemic lupus erythematosus with death from acute pulmonary hemorrhage].

An autopsy case of SLE died from acute and diffuse pulmonary hemorrhage is presented. A 50 year-old woman with SLE was admitted to our hospital because of high fever, butterfly rash, discoid skin lesions and renal dysfunction. She died from acute respiratory failure before initiation of the therapy with corticosteroid. Autopsy findings revealed a massive acute intrapulmonary hemorrhage. Histological study demonstrated a pulmonary arterial vasculitis with prominent fibrinoid necrosis at muscular pulmonary artery. No remarkable deposit of immunoglobulins and complements was found within the alveolar walls and pulmonary vessels by immunofluorescence and electron microscopy. Renal histology revealed diffuse proliferative glomerulonephritis with fibrinoid necrosis, crescent formation and wireloop lesions compatible with type IVb according to the WHO classification. The granular deposit of IgM, C3 and Clq, and electron dense deposit was found by immunofluorescence and by electron microscopy, respectively, in the kidney. The small arteries and veins in other organs, such as liver, spleen, bladder, ovary and rectum also revealed fibrinoid vasculitis. Acute infectious lesion was not observed in any tissue examined. The diffuse pulmonary hemorrhage in SLE could be one of the manifestations of active and severe systemic vasculitis.

Acute Disease↗

Menkes' kinky hair disease: morphological and immunohistochemical comparison of two autopsied patients.

An autopsied patient with Menkes' kinky hair disease, who showed unusually long survival until the age of five years with typical neuropathological changes, was examined for distribution of neuronal depletion in the cerebral cortex, and the cerebellar changes were compared morphologically and immunohistochemically with those found in a younger patient (1 year 8 months old) reported previously. Neuronal loss in the cerebral cortex in the both cases, which was ill-defined and unassociated with gliosis, was preferentially distributed in the fifth and sixth layers, especially of the gyral bottom in almost all lobes in the older case. Therefore, this change was thought to be secondary to local ischemia caused by mechanical distortion at the stage of gyrus formation in addition to abnormal development. Ultrastructurally, a prominent increase of confronting cisternae (CC) complexes was found in the perikaryon and processes of Purkinje cells in both cases, and in the older patient CC complexes were arranged more densely and were transformed into concentric lamellar structures in the swollen dendrites. Immunohistochemically, the stainability of neurofilaments (NF, 200 kDa) in Purkinje cells, with or without somatic sprouts was faint or negative in the older patient compared with the marked or moderate positivity in the younger patient and age-matched controls. Empty baskets were absent and NF-positive axonal terminals and synaptophysin-positive granules on Purkinje cells were markedly decreased in both cases. These changes suggest that Purkinje cells degenerate progressively with time and that basket cells also are simultaneously involved.

Autopsy↗

Neuropathology of the central nervous system in acquired immune deficiency syndrome (AIDS) in Japan. With special reference to human immunodeficiency virus-induced encephalomyelopathies.

The neuropathological features of the central nervous system in 15 autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono- and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.

AIDS Dementia Complex↗

Accumulation of oedema fluid in deep white matter after cerebral cold injury.

The distribution of oedema fluid was examined in cats subjected to a cryogenic cortical injury. The lesion was made in the parietal cortex, and the animals were sacrificed 6 hr after the injury. The serum concentration of 125I bovine serum albumin was kept constant over the 6 hr period by a programmed infusion. Autoradiograms were made from the coronal sections through the lesion and were used to quantify densitometrically the regional content of extravasated serum albumin. After autoradiographic exposure, the section was stained with luxol-fast blue (LFB), and the degree of LFB discoloration was quantified. The maximal accumulation of extravasated serum albumin was observed in the deeper white matter under the subcortical white matter and not in the subcortical white matter of the lesion. The degree of oedema indicated by LFB discoloration showed a similar distribution pattern. This indicates that the compliance of the white matter in vasogenic oedema is regionally different. This difference of regional compliance seems to depend on the structural characteristics of each region such as the type of the fibers and the orientation of the fibers.

Animals↗

Experimental neurotoxicity of 5-fluorouracil and its derivatives is due to poisoning by the monofluorinated organic metabolites, monofluoroacetic acid and alpha-fluoro-beta-alanine.

Two metabolites of 5-fluorouracil (FU), monofluoroacetic acid (FA) and alpha-fluoro-beta-alanine (FBAL), were continuously administered into the left ventricle of the brain in cats for up to 1 month to investigate the mechanism of neurotoxicity of FU and its derivatives. The cumulative doses of FU and FBAL over a 1-month period were 1.5-45 mg (20 cats) and 0.2-4.8 mg (21 cats), respectively. As controls for each experimental group, acetic acid (AA) and beta-alanine (BAL) were administered. In terms of survival time in relation to the cumulative dose and molecular weight, FBAL was more toxic than FA. Neuropathologically, two types of change, vacuoles and necrosis/softening-like change, were found. The vacuoles were 20-50 microns in diameter, and distributed mainly in the cerebellar nuclei, white matter and the tectum and tegmentum of the brain stem in both experimental groups. Electron microscopically, these vacuoles were due to splitting of the myelin intraperiod line or separation between the axon and the innermost layer of myelin. Necrosis/softening-like change occurred preferentially in the FBAL group and was located symmetrically in the superior and inferior colliculi, oculomotor nuclei and thalamus. Both types of neuropathological change, especially those in the FBAL group, were similar to those found in cats orally administered with FU and its derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multifocal vacuolar leucoencephalopathy: a distinct HIV-associated lesion of the brain.

A 20-year-old male AIDS patient developed rapidly progressive dementia for more than 3 months prior to death. Autopsy showed, in addition to adrenal cytomegalovirus (CMV) infection and focal cerebral necrosis due to toxoplasmosis, multifocal subcortical white matter lesions of the brain which were strikingly similar to the histopathology of vacuolar myelopathy in AIDS. These distinct lesions contained macrophages which were rarely multinucleated and expressed HIV antigens by immunocytochemistry. The distribution of lesions mimics extrapontine myelinolysis and progressive multifocal leucoencephalopathy (PML); PML was excluded by the absence of papovaviruses by immunocytochemistry and by in situ DNA hybridization. Tissue damage in multifocal vacuolar leucoencephalopathy is different from hitherto characterized HIV-specific neuropathology such as HIV encephalitis and HIV leucoencephalopathy, and should be included in the list of conditions with damage of the brain white matter in AIDS.

AIDS Dementia Complex↗

Hydrostatic pressure versus osmotic pressure in the development of vasogenic brain edema induced by cold injury.

The role of hydrostatic pressure and osmotic pressure gradient in the development of vasogenic brain edema induced by cold lesion made in the parietal cortex was studied in cats under ketamine anesthesia and blood pressure monitoring. The animals were divided into a hypertensive group and a normotensive group and were kept alive for 6 hr. The brain was removed and cut coronally at the lesion for tissue sampling from various areas of edematous white matter to measure both the SG and the amount of extravasated serum albumin in the same samples. Our result showed that the edema confined in the area containing extravasated serum albumin and the increase of water content correlated linearly with the amount of extravasated serum albumin both in the normotensive group and hypertensive group. However, the slope of the regression line indicated albumin content in the edema fluid was significantly different between the two groups. The slope became lower as the MABP during the experiment became higher, indicating that protein concentration in the edema fluid became lower when hypertension sustained. Thus, both hydrostatic and osmotic pressure gradient regulate the extravascular accumulation of edema fluid in the cold lesion edema.

Albumins↗

Methotrexate-related multifocal axonopathy. Report of an autopsy case.

A case of multifocal axonopathy associated with intrathecal methotrexate (IT MTX) and radiation therapy is presented. A 33-year-old woman suffering from meningeal carcinomatosis of breast cancer origin had developed prominent multifocal axonal degeneration in the cerebral white matter after treatment with IT MTX therapy and cranial irradiation. The principal features of this axonal degeneration were segmental hydropic swellings, macrophage infiltration of swollen axons, and scattered spheroid formation associated with reactive astrocytosis. These features were similar to those observed in our previous experimental study using cats treated with IT MTX alone. This "multifocal axonopathy" without necrotizing lesions seems to be different from disseminated necrotizing leukoencephalopathy, and, therefore, may be another form of MTX-related leukoencephalopathy. IT MTX and cranial irradiation seem to have exerted synergistic effects in producing the "multifocal axonopathy" in this case.

Adult↗

Adult-type citrullinemia.

An autopsy case of adult-type citrullinemia in a 42-year-old male is reported. The patient neuropathologically presented mixed cerebral changes consisting of the pseudoulegyric and ischemic types of hepatocerebral disease. In common with previously reported cases of the pseudoulegyric type, the nature and localization of the cerebral changes in this case were characteristic, in that neuronal loss occurred most severely and symmetrically in the mediobasal part of the frontal and occipital lobes, gyrus cinguli, claustrum, insula and temporal lobe, and that the watershed area of the cerebral cortex, basal ganglia and Purkinje cells were only slightly affected. The importance of hypercitrullinemia was stressed in the pathogenesis of the cerebral changes evident in adult-type citrullinemia.

Adult↗

Adult pigment type (Peiffer) of sudanophilic leukodystrophy. Pathological and morphometrical studies on two autopsy cases of siblings.

Two autopsy cases of siblings with the adult pigment (Peiffer) type of sudanophilic leukodystrophy (SLD), which demonstrated the full-blown stage (case 1) and early stage (case 2) of demyelination, were examined. Numerous brown pigments deposited in demyelinated cerebral areas were characterized histochemically and ultrastructurally as lipofuscin and ceroid. Under the electron microscope formation of blebs due to myelin splitting associated with deposition of multilamellar myeloid bodies within them was a prominent feature in the demyelinated cerebral areas of case 2 as compared with case 1. However, various features of myelin degradation such as thinning, partial or complete circumferential myelin loss, and deposition of electron-dense material on the interperiodic lines were found in both cases. Blebs occurred in all layers of myelin, and axons were compressed by these blebs or the hydropically swollen inner lips of oligodendroglias. Oligodendroglias were relatively well preserved in the demyelinated and nondemyelinated areas in case 2, although the cytoplasm was hydropic. Many spheroids were present in demyelinated areas and were irregularly distributed in both cases. The peripheral nerves in case 1 presented essentially the same changes as those in the brain, although those in case 2 were not affected. Morphometrically, the results showed that hypomyelination was not the mechanism for this pigment type of SLD. One possible cause may be an accelerated ageing of the metabolic process of myelin turnover.

Astrocytes↗