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Eisaku Ohama

Publications and source records attributed to Eisaku Ohama.

At least 19 recordsLinked to original sources
PubMed2006

Fragmentation of Golgi apparatus of nigral neurons with alpha-synuclein-positive inclusions in patients with Parkinson's disease.

We examined whether the Golgi apparatus (GA) is fragmented in nigral neurons in 18 cases with Parkinson's disease (PD) and in 8 control cases. The nigral neurons in cases with PD showed various degrees of Lewy pathology with alpha-synuclein immunohistochemistry, and we divided the neurons into three subtypes according to differences in alpha-synuclein immunoreactivity: (1) neurons without pale bodies or Lewy bodies, (2) neurons with pale bodies, and (3) neurons with Lewy bodies. In controls, we did not observe fragmented GA in nigral neurons by immunocytochemistry with an anti-TGN46 antibody. In PD, the GA was fragmented in 3% of the nigral neurons without inclusions, and in 5% of the neurons with Lewy bodies. In contrast, fragmented GA was noted in 19% of the neurons containing pale bodies. Since pale bodies represent early stages in the development of brainstem Lewy bodies, our results suggest that the cytotoxicity of alpha-synuclein-positive aggregates is reduced in the process of Lewy body formation.

Aged↗
PubMed2006

Nestin immunoreactivity of Purkinje cells in Creutzfeldt-Jakob disease.

Nestin, an intermediate filament protein, is mainly expressed in neural progenitor/stem cells in the central nervous system. Recently, we reported that nestin is expressed in Purkinje cells in patients with Creutzfeldt-Jakob disease (CJD). In this study, we examined a total of 19 CJD cerebella to analyze the intensity and pattern of nestin immunoreactivity of Purkinje cells in different pathological stages of degeneration in the cerebellar cortex. The results showed that the Purkinje cells were immunoreactive with nestin regardless of the severity of degenerative cerebellar cortex. Furthermore, we noted several different types of nestin immunoreactivity, indicated by diffuse and fine, coarse, and inclusion-like immunostainings within Purkinje cell bodies as well as dot-like staining outside of the cell bodies. In contrast, on examination of cerebella from non-CJD patients, 6 of 30 cases showed nestin immunoreactivity to a lesser extent. Thus, nestin-positive Purkinje cells are more common in CJD cerebella than in non-CJD cerebella. Although the mechanism of nestin expression in Purkinje cells is not yet understood, we suggest that such nestin-positive Purkinje cells are being reactivated to survive the cell death.

Adolescent↗
PubMed2006

A case of Tolosa-Hunt syndrome affecting both the cavernous sinuses and the hypophysis, and associated with C3 and C4 aneurysms.

BACKGROUND: We describe the first case of Tolosa-Hunt syndrome that is associated with C3 and C4 aneurysms. CASE DESCRIPTION: The patient, a female aged 58 years, had diplopia and right retroorbital pain. Magnetic resonance imaging revealed an enlargement of the hypophysis and bilateral cavernous sinuses, particularly on the right side. Cerebral angiography demonstrated ICA aneurysms of the left C3 and right C4 portions. These symptoms were immediately alleviated after initiation of prednisolone therapy, but recurred after the dose was tapered off. Radiological examination revealed an enlargement of the hypophysis whereas the right C4 aneurysm had decreased in size and no blood flow was apparent in the ipsilateral ophthalmic artery. A biopsy was performed and the results showed a focal inflammatory change. Steroid therapy was represcribed, and after a follow-up period of 10 months without therapy, the patient has been free of symptoms. CONCLUSION: We conclude that bilateral ICA aneurysms might be directly induced by inflammatory infiltration into intracavernous ICAs.

Carotid Artery Diseases↗
PubMed2006

White matter changes in elderly people: MR-pathologic correlations.

Magnetic resonance (MR) imaging features of white matter lesions, often seen in the elderly, are correlated with histologic findings. Dilatation of perivascular spaces is seen, especially in the frontal and/or parietal subcortical white matter; the spaces are less than 3 mm in diameter and have sharp margins with no perifocal abnormality. Old lacunar infarcts are larger than 3 mm in diameter and are irregularly shaped and accompanied by perifocal myelin pallor and gliosis. Periventricular hyperintensity, including cap and rim, histologically shows myelin pallor, dilatation of perivascular spaces, discontinuity of the ependymal lining, and subependymal gliosis. Deep and subcortical white matter hyperintensity reflects myelin pallor and dilatation of perivascular spaces. Diffuse white matter lesion, seen in Binswanger's disease, shows myelin pallor and tissue rarefaction associated with loss of myelin and axons. U-fibers are usually well preserved. Severe arteriosclerosis and arteriolosclerosis are usually seen in the white matter. Knowledge of the pathologic features of incidental changes in white matter helps in understanding MR imaging findings.

Aged↗
PubMed2005

Redox system expression in the motor neurons in amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS, superoxide dismutase 1 (SOD1)-mutated familial ALS, and SOD1-mutated ALS animal models.

Peroxiredoxin-ll (Prxll) and glutathione peroxidase-l (GPxl) are regulators of the redox system that is one of the most crucial supporting systems in neurons. This system is an antioxidant enzyme defense system and is synchronously linked to other important cell supporting systems. To clarify the common self-survival mechanism of the residual motor neurons affected by amyotrophic lateral sclerosis (ALS), we examined motor neurons from 40 patients with sporadic ALS (SALS) and 5 patients with superoxide dismutase 1 (SOD1)-mutated familial ALS (FALS) from two different families (frame-shift 126 mutation and A4 V) as well as four different strains of the SOD1-mutated ALS models (H46R/G93A rats and G1H/G1L-G93A mice). We investigated the immunohistochemical expression of Prxll/GPxl in motor neurons from the viewpoint of the redox system. In normal subjects, Prxll/GPxl immunoreactivity in the anterior horns of the normal spinal cords of humans, rats and mice was primarily identified in the neurons: cytoplasmic staining was observed in almost all of the motor neurons. Histologically, the number of spinal motor neurons in ALS decreased with disease progression. Immunohistochemically, the number of neurons negative for Prxll/GPxl increased with ALS disease progression. Some residual motor neurons coexpressing Prxll/GPxl were, however, observed throughout the clinical courses in some cases of SALS patients, SOD1-mutated FALS patients, and ALS animal models. In particular, motor neurons overexpressing Prxll/GPxl, i.e., neurons showing redox system up-regulation, were commonly evident during the clinical courses in ALS. For patients with SALS, motor neurons overexpressing Prxll/GPxl were present mainly within approximately 3 years after disease onset, and these overexpressing neurons thereafter decreased in number dramatically as the disease progressed. For SOD1-mutated FALS patients, like in SALS patients, certain residual motor neurons without inclusions also overexpressed Prxll/GPxl in the short-term-surviving FALS patients. In the ALS animal models, as in the human diseases, certain residual motor neurons showed overexpression of Prxll/GPxl during their clinical courses. At the terminal stage of ALS, however, a disruption of this common Prxll/GPxl-overexpression mechanism in neurons was observed. These findings lead us to the conclusion that the residual ALS neurons showing redox system up-regulation would be less susceptible to ALS stress and protect themselves from ALS neuronal death, whereas the breakdown of this redox system at the advanced disease stage accelerates neuronal degeneration and/or the process of neuronal death.

Adult↗
PubMed2005

Clinically silent choroid plexus cyst: evaluation by diffusion-weighted MRI.

We retrospectively reviewed diffusion-weighted magnetic resonance images of 57 patients with a choroid plexus cyst diagnosed by contrast-enhanced T1-weighted imaging. All the cysts appeared to represent incidental findings. Thirty-eight of 57 patients had bilateral cysts and 19 had unilateral ones. On diffusion-weighted images, 78 of 95 cysts showed homogeneously high signal intensity, 12 showed focal high signal areas, and 5 had no portion with a high signal. The apparent diffusion coefficient of the high signal areas in the cysts was (1.46+/-0.14) x10(-3) mm(2)/s, intermediate between the apparent diffusion coefficients of cerebrospinal fluid and cerebral white matter, (3.15+/-0.67) x10(-3) and (0.79+/-0.22) x10(-3) mm(2)/s, respectively. Pathological correlation was available in one case, showing high signal intensity areas in the glomera of the choroid plexuses in the lateral ventricles on diffusion-weighted images corresponding to gelatinous cysts with highly proteinaceous content.

Adult↗
PubMed2005

Pro-apoptotic protein glyceraldehyde-3-phosphate dehydrogenase promotes the formation of Lewy body-like inclusions.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro-apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild-type or mutant (A53T) alpha-synuclein and less likely with beta-synuclein in transfected COS-7 cells was found to induce Lewy body-like cytoplasmic inclusions. Unlike its full-length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin- and thioflavin S-positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild-type alpha-synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro-apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.

Acetates↗
PubMed2005

Application of energy-dispersive X-ray microanalysis on the diagnosis of atypical calcific band keratopathy.

We describe pathological, ultrastructural, and spectrographic analyses of surgically resected cornea from a man with atypical corneal opacification, and discuss the corneal pathogenesis, and the utility of energy-dispersive X-ray microanalysis (EDXA). The histopathologic features of a case presenting with longstanding bilateral corneal clouding are reported, which was difficult to be diagnosed clinically as calcific band keratopathy. The patient underwent keratoplasty on his right eye. Paraffin sections of the host corneal button were subjected to hematoxylin and eosin (H&E). An adjacent section was studied by means of EDXA. Plastic sections were observed under a transmission electron microscope (TEM). H&E staining revealed flattened corneal epithelial cells and disappearing Bowman's membrane accompanied by numerous basophilic granular deposits within the underlying corneal stroma. EDXA demonstrated the elevated peaks of calcium and phosphorus within the area of granular deposits. TEM revealed electron dense material consistent with extracellular calcospherites. Given the patient's past medical and family history, and the serologic test results, the clinical presentation and histological findings were most consistent with calcific band keratopathy associated with preexisting minimal syphilitic keratitis. Extensive histologic studies including EDXA on resected corneal tissue can be helpful for the differential diagnosis and may elucidate the pathogenesis of corneal diseases.

Aged↗
PubMed2005

Cerebral cortical and white matter lesions in chronic hepatic encephalopathy: MR-pathologic correlations.

We correlated MR images with histologic findings in two autopsy-proven cases of chronic hepatic encephalopathy. Cortical hyperintensities on T2-weighted images histologically revealed pseudolaminar spongy degeneration in the deep layers of the cerebral cortices and hyperintensities in the cerebral white matters showed tissue rarefaction associated with loss of myelin and axons but without reactive astrocytosis. Both lesions were considered to be caused by chronic hepatic encephalopathy.

Aged↗
PubMed2005

[Hemangioendothelioma of the brain presenting with intracerebral hemorrhage: a case report].

Hemangioendothelioma (HE) is an uncommon vascular tumor that is intermediate in histological appearance between a hemangioma and an angiosarcoma. Presently, it is regarded as endothelial tumors of low-grade or intermediate malignancy. It has been reported in the liver, lung, heart, mediastinum, lymph nodes, extremity, and bone. The occurrence in the brain is extremely rare; only 16 cases have so far been reported. We report a 51-year-old woman who presented with transient visual disturbance and weakness of the left upper limb on April 12th 2003. Computed tomography (CT) revealed a high density mass in the right parietal lobe. In magnetic resonance imaging (MRI), the lesion is hyperintense on TIWI, isointense on T2WI, and no enhancement with gadopentetate dimegliumine. Intratumoral hemorrhage was indicated and preoperative diagnosis was cavernous angioma. The tumor was excised completely on April 28th 2003. Pathologically, the tumor cells resembled endothelial cells, positive immunoreactivity for Factor VIII, and grew in small nests or cords. Postoperative MRI showed complete removal of the tumor. There has been no recurrence for 8 months after the surgery, but we have to follow MRI up for a long time. We discussed intracerebral HE clinically and neuroradiologically.

Brain Neoplasms↗
PubMed2004

Expression of ubiquitin-binding protein p62 in ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis with dementia: analysis of five autopsy cases with broad clinicopathological spectrum.

Amyotrophic lateral sclerosis with dementia (ALSD), corresponding to the motor neuron disease type of frontotemporal dementia, is neuropathologically characterized by depletion of the motor neurons, degeneration of the extra-motor cerebral cortices and formation of ubiquitin-immunoreactive (not argyrophilic, tau-negative, alpha-synuclein-negative) intraneuronal inclusions. Recently, immunoreactivity for ubiquitin-binding protein p62 has been reported in several ubiquitin-containing intraneuronal or intraglial inclusions (e.g. neurofibrillary tangles, Pick bodies, Lewy bodies, glial cytoplasmic inclusions) in various neurodegenerative diseases. We examined p62 immunoreactivity in ubiquitin-immunoreactive intraneuronal inclusions in five ALSD cases with a broad clinicopathological spectrum. p62 immunoreactivity in ubiquitin-immunoreactive intraneuronal inclusions was seen in all cases. The mean proportion of p62-immunoreactive inclusions to the total number of ubiquitin-immunoreactive inclusions (p62/Ub ratio) in the dentate gyrus was 27.5 +/- 16.6% (range 6.3-47.3%). There was no correlation between p62/Ub ratio and the severity of dementia, duration of illness or neuropathological severity. Although the main constituent of these inclusions is unknown, our study suggests that p62 contributes to the formation of the inclusions via the same mechanism as in other previously reported neurodegenerative diseases. Since p62 is believed to have a neuroprotective role, the formation of these inclusions may represent a non-harmful, rather protective effect against the neuronal degeneration in ALSD.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Attenuation of vascularity by preoperative radiosurgery facilitates total removal of a hypervascular hemangioblastoma at the cerebello-pontine angle: case report.

BACKGROUND: The surgical removal of solid, large, and deep-seated hemangioblastomas remains challenging because it is difficult to control bleeding during the procedure. We used preoperative radiosurgery in a solid, highly vascular hemangioblastoma at the left cerebello-pontine angle and present our angiographic, operative, and histologic findings. CASE DESCRIPTION: A 37-year-old paraplegic woman with multiple hemangioblastomas was re-admitted to our clinic with cerebellar ataxia 6 years after resection of a tumor at the fourth ventricle. A vertebral artery angiogram revealed that the 3.5 cm diameter hemangioblastoma at the left cerebello-pontine angle was highly vascular and fed by the left anterior inferior cerebellar artery and posterior inferior cerebellar artery. Nine months before surgical removal it was treated with stereotactic radiosurgery (gamma knife, margin dose 28 Gy) to inhibit tumor progression and to reduce its vascularity. The tumor was totally removed via the left lateral suboccipital approach; bleeding was well controlled and there were no complications. Pathologic examination of the content of the excised tumor revealed coagulation necrosis with hyaline degeneration of the tumor vessels, resulting in a marked decrease in its vascularity. CONCLUSION: Preoperative radiosurgery led to a marked reduction in the vascularity of this hypervascular hemangioblastoma and was useful for controlling bleeding from the tumor during resection. We succeeded to remove the vascular-rich hemangioblastma after the intentional preoperative radiosurgery. The pathologic changes induced by radiotherapy were confirmed by operative finding.

Adult↗
PubMed2003

Histological evidence of redox system breakdown caused by superoxide dismutase 1 (SOD1) aggregation is common to SOD1-mutated motor neurons in humans and animal models.

Living cells produce reactive oxygen species (ROSs). To protect themselves from these ROSs, the cells have developed both an antioxidant system containing superoxide dismutase 1 (SOD1) and a redox system including peroxiredoxin2 (Prx2, thioredoxin peroxidase) and glutathione peroxidase1 (GPx1): SOD1 converts superoxide radicals into hydrogen peroxide (H2O2), and H2O2 is then converted into harmless water (H2O) and oxygen (O2) by Prx2 and GPx1 that directly regulate the redox system. To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations. The LBHIs in motor neurons from the SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2 and GPx1: the reaction product deposits with the antibodies against Prx2 and GPx1 were localized in the LBHIs. In addition, the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 were similar in the inclusions: the co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic rats was evident. Based on the fact that Prx2/GPx1 directly regulates the redox system, such co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the redox system itself, thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1.

Adult↗
PubMed2003

Bcl-2 expression using retrograde transport of adenoviral vectors inhibits cytochrome c-release and caspase-1 activation in motor neurons of mutant superoxide dismutase 1 (G93A) transgenic mice.

We explored a possible mechanism of the neuro-protective effects of exogenous human Bcl-2 expression on motor neurons of transgenic mice expressing human Cu/Zn superoxide dismutase with a G93A mutation (G93A mice), using retrograde transport and a Cre-loxP recombination system employing adenoviral vectors. We examined the cellular localization of cytochrome c and caspase-1 using immunohistochemical study, in motor neurons of hypoglossal nuclei of G93A mice at 15 weeks after inoculation with the adenoviral vectors, at which time over-expressed exogenous Bcl-2 declined to reach the baseline of intrinsic Bcl-2. We found that a significant number of neurons showed more faint and punctate immunostaining against cytochrome c and significantly less neurons showed immunoreactivity against activated caspase-1, compared with those of mice without inoculation. These results suggest that transient exogenous Bcl-2 expression at the early stage of the disease protects against motor neuronal degeneration in G93A mice by retarding translocation of cytochrome c into the cytosol, and regulating caspase-1 for a substantial period.

Adenoviridae↗
PubMed2003

Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene.

A number of chromosomal abnormalities including 19q deletions have been associated with the formation of human gliomas. In this study, we employed a proteomics-based approach to identify possible genes involved in glioma tumorigenesis which may serve as potential diagnostic molecular markers for this type of cancer. By comparing protein spots from gliomas and non-tumor tissues using two-dimensional (2D) gel electrophoresis, we identified 11 up-regulated proteins and four down-regulated proteins in gliomas. Interestingly, we also discovered that a group of cytoskeleton-related proteins are differentially regulated in gliomas, suggesting the involvement of cytoskeleton modulation in glioma pathogenesis. We then focused on the cytoskeleton-related protein, SIRT2 (sirtuin homologue 2) tubulin deacetylase, which was down-regulated in gliomas. SIRT2 is located at 19q13.2, a region known to be frequently deleted in human gliomas. Subsequent Northern blot analysis revealed that RNA expression of SIRT2 was dramatically diminished in 12 out of 17 gliomas and glioma cell lines, in agreement with proteomic data. Furthermore, ectopic expression of SIRT2 in glioma cell lines led to the perturbation of the microtubule network and caused a remarkable reduction in the number of stable clones expressing SIRT2 as compared to that of a control vector in colony formation assays. These results suggest that SIRT2 may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network and may serve as a novel molecular marker for gliomas. Additional proteins were also identified, whose function in gliomas was previously unsuspected.

Blotting, Northern↗
PubMed2003

Expression of hepatocyte growth factor and c-Met in the anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation.

To clarify the trophic mechanism of residual anterior horn cells affected by sporadic amyotrophic lateral sclerosis (SALS) and familial ALS (FALS) with superoxide dismutase 1 (SOD1) mutations, we investigated the immunohistochemical expression of hepatocyte growth factor (HGF), a novel neurotrophic factor, and its receptor, c-Met. In normal subjects, immunoreactivity to both anti-HGF and anti-c-Met antibodies was observed in almost all anterior horn cells, whereas no significant immunoreactivity was observed in astrocytes and oligodendrocytes. Histologically, the number of spinal anterior horn cells in ALS patients decreased along with disease progression. Immunohistochemically, the number of neurons negative for HGF and c-Met increased with ALS disease progression. However, throughout the course of the disease, certain residual anterior horn cells co-expressed both HGF and c-Met with the same, or even stronger intensity in comparison with those of normal subjects, irrespective of the reduction in the number of immunopositive cells. Western blot analysis revealed that c-Met was induced in the spinal cord of a patient with SALS after a clinical course of 2.5 years, whereas the level decreased in a SALS patient after a clinical course of 11 years 5 months. These results suggest that the autocrine and/or paracrine trophic support of the HGF-c-Met system contributes to the attenuation of the degeneration of residual anterior horn cells in ALS, while disruption of the neuronal HGF-c-Met system at an advanced disease stage accelerates cellular degeneration and/or the process of cell death. In SOD1-mutated FALS patients, Lewy body-like hyaline inclusions (LBHIs) in some residual anterior horn cells exhibited co-aggregation of both HGF and c-Met, although the cytoplasmic staining intensity for HGF and c-Met in the LBHI-bearing neurons was either weak or negative. Such sequestration of HGF and c-Met in LBHIs may suggest partial disruption of the HGF-c-Met system, thereby contributing to the acceleration of neuronal degeneration in FALS patients.

Adult↗