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Asao Hirano

Publications and source records attributed to Asao Hirano.

At least 19 recordsLinked to original sources
PubMed2006

Fine structure of neuronal and glial processes in neuropathology.

The cells of the nervous system are characterized by their well-formed cell processes and by cell-to-cell relationships that they form. The neuron reveals essentially cylindrical processes, which form synaptic junctions. On the other hand, the peripheral parts of the glial cells are mainly sheet-like in nature. Thus, the oligodendroglial cell elaborates many sheet-like processes, each of which forms a segment of the myelin sheath. Unique cell junction, transverse bands are present at the interface of oligodendroglial processes and the axon. Finally, the astrocytes also form elaborate sheet-like processes, which separate most of the CNS from the mesodermal tissue as well as surrounding certain neuronal surfaces, including synapses. Punctate adhesions, gap junctions and other adhesive devices are present between astrocytic processes. Defects or anomalies in the neuronal and glial cell processes characterize numerous pathological conditions.

Animals↗
PubMed2006

Topographic study of Alzheimer's neurofibrillary changes: a personal perspective.

Argentophilic neurofibrillary tangles were described in the cerebral cortex of Alzheimer's disease and later in the pigmented neurons in the brain stem of postencephalitic parkinsonism. In 1961, wide distribution of Alzheimer's neurofibrillary tangles in the central nervous system was observed in endemic fatal neurodegenerative diseases affecting the native Chamorro population on Guam: amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam. Abundant neurofibrillary tangles were found but no senile plaques. A topographic analysis of tangles in cases in Guam and at Montefiore were published in 1962. Thereafter, Alzheimer's neurofibrillary changes were documented in various areas of the nervous system of many other diseases. This communication is a brief review of the topographic investigation of Alzheimer's neurofibrillary changes. Occurrence of tangles in various conditions seems to indicate that various pathological agents can induce tangles. On the other hand, Alzheimer's neurofibrillary tangles, in general, show a rather striking predilection to affect particular neurons in the involved regions.

Alzheimer Disease↗
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

The role of electron microscopy in neuropathology.

The electron microscope has been an essential instrument for elucidating the morphology of cells and tissue. Fine structural investigation of nervous tissue has disclosed numerous new findings, which were once invisible. In this communication I present my personal perspective on the role of electron microscopy in neuropathology through the presentation of selected electron microscopic projects engaged in our institution. These include brain edema, structural analysis of the myelin in the central nervous system, endodermal cysts in the central nervous system, aberrant synaptic development, toxoplasmosis in AIDS, and Hirano bodies.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Functional anatomy of the basal ganglia in X-linked recessive dystonia-parkinsonism.

Dystonia is a neurological syndrome characterized by sustained muscle contractions that produce repetitive twisting movements or abnormal postures. X-linked recessive dystonia parkinsonism (XDP; DYT3; Lubag) is an adult-onset disorder that manifests severe and progressive dystonia with a high frequency of generalization. In search for the anatomical basis for dystonia, we performed postmortem analyses of the functional anatomy of the basal ganglia based on the striatal compartments (ie, the striosomes and the matrix compartment) in XDP. Here, we provide anatomopathological evidence that, in the XDP neostriatum, the matrix compartment is relatively spared in a unique fashion, whereas the striosomes are severely depleted. We also document that there is a differential loss of striatal neuron subclasses in XDP. In view of the three-pathway basal ganglia model, we postulate that the disproportionate involvement of neostriatal compartments and their efferent projections may underlie the manifestation of dystonia in patients with XDP. This study is the first to our knowledge to show specific basal ganglia pathology that could explain the genesis of dystonia in human heredodegenerative movement disorders, suggesting that dystonia may result from an imbalance in the activity between the striosomal and matrix-based pathways.

Adult↗
PubMed2004

Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis.

4-Hydroxy-2-hexenal (HHE) is a toxic, reactive aldehydic intermediate formed by nonenzymatic peroxidation of n-3 polyunsaturated fatty acids. The aim of this study was to determine the implication for HHE in the pathomechanism of amyotrophic lateral sclerosis (ALS) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) techniques using a mouse monoclonal IgG(1) antibody mAbHHE53 specific for protein-bound HHE. Immunohistochemical analysis on formalin-fixed, paraffin-embedded sections and frozen sections of spinal cords obtained at autopsy from 10 sporadic ALS patients and 10 age-matched control subjects demonstrated that protein-bound HHE immunoreactivity was seen and was prominent in the entire gray matter in the ALS cases and localized in the neurons, reactive astrocytes, microglial cells, and the surrounding neuropil, while the immunoreactivity was obscure or undetectable in the control cases. No significant protein-bound HHE immunoreactivity was seen in sections processed with omission of mAbHHE53 or in sections incubated with the antibody with an excess of the respective antigen. Competitive ELISA analysis on trypsin-digested protein extracts of fresh-frozen spinal cord samples disclosed a significant increase in protein-bound HHE level in the ALS cases compared with the control cases. Our results indicate that enhanced HHE formation occurs in the entire gray matter of sporadic ALS spinal cords and suggest that the selective vulnerability of motor neurons to HHE mediates the pathomechanism of this disease.

Aged↗
PubMed2004

A human granin-like neuroendocrine peptide precursor (proSAAS) immunoreactivity in tau inclusions of Alzheimer's disease and parkinsonism-dementia complex on Guam.

The deposition of tau inclusions is one of the neuropathological hallmarks in neurodegenerative disorders with dementia. We have reported that the N-terminal fragment of a human granin-like neuroendocrine peptide precursor (N-proSAAS) is accumulated in Pick bodies. However, it is unknown whether N-proSAAS is widely accumulated in tau inclusions in other tauopathies. Here, we performed an immunohistochemical examination using antibodies against both the N- and C-terminal sequence of proSAAS in the brains of patients with Alzheimer's disease and parkinsonism-dementia complex on Guam. The antibody against N-proSAAS immunostained neurofibrillary tangles and neuritic plaques in both diseases, whereas the antibody against the C-terminal sequence of proSAAS did not. The results of the present study suggest that N-proSAAS or proSAAS-like molecules were trapped within the tau fibrils and accumulated in tau inclusions.

Aged↗
PubMed2004

Benign cysts in the central nervous system: neuropathological observations of the cyst walls.

A diverse variety of benign cysts exist in the CNS. Advances in diagnostic radiology have facilitated diagnoses and surgical intervention in many patients with CNS cysts. However, a fundamental understanding of the pathological features of these lesions is clinically vital. From an etiological point of view, the cysts can be divided into two groups. The first includes lesions that arise from within the CNS and may be static structures such as cavities arising from infarcts and other destructive processes while other lesions such as arachnoid cysts, ependymal cysts, cystic hemangioblastoma, cystic cerebellar astrocytoma and infectious processes, are progressive. The second group of cysts arise from the intrusion of non-nervous system tissue into the neuroaxis and are usually midline. They are frequently expanding congenital lesions although some become symptomatic only in adults. Examples include teratomas, dermoid cysts, epidermoid cysts, craniopharyngiomas, Rathke's cleft cysts, and other epithelial cysts presumably derived from the upper respiratory or intestinal tract. Chick embryos exposed to lead have been used as a model of cyst formation.

Animals↗
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

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↗
PubMed2003

[Changes in neurological diseases during the last half century. Neuropathological view point].

Environmental changes are intensifying at an increasing tempo along with the advance of civilization. The appearance change and disappearance of certain diseases are remarkable. The author has been studying the neuropathology of fatal neurodegenerative diseases endemic to the native Chamorro population on Guam during the last half century. During this time, significant advances in scientific technology, such as electron microscopy, immunohistochemistry and molecular biology has contributed to an impressive development of neuropathology. Many new findings have been discovered allowing delineation of additional disease entities. In addition, many new neurological disorders have appeared. This communication reviews clinicopathology of amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam as well as improvement of the nervous system as a complication of AIDS studied at Montefiore Medical Center in New York.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in human brain tumors: relationships of iNOS to superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein.

In this study, inducible nitric oxide synthase (iNOS) expression in a series of 158 human primary brain tumors was analyzed. To gain some insight into the biological significance of iNOS expression in tumor cells, comparative immunohistochemical analyses were employed to characterize the expression of iNOS, superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein in these cells. Sixteen (39.0%) of the 41 glioblastoma multiforme (GBM) specimens showed iNOS immunoreactivity. Positive immunoreactions with iNOS were also detected in 2/8 anaplastic astrocytomas, 1/17 astrocytomas, 1/14 medulloblastomas and 1/11 primitive neuroectodermal tumors, but no positive reactions were observed in oligodendrogliomas (0/11), ependymomas (0/5), schwannomas (0/21), meningiomas (0/23) or pituitary adenomas (0/7). The MIB-1 labeling index of GBMs that expressed iNOS was significantly higher than that of GBMs that did not (0.025< P <0.05, Wilcoxon rank-sum test). Unlike iNOS-negative tumors, all iNOS-positive tumors coexpressed SOD1 or SOD2. In particular, there was a significant correlation between iNOS induction and SOD1 expression (P =1.65x10(-10), Fisher's exact test) in GBM specimens. There was no significant relationship between iNOS and p53 protein in any type of primary brain tumor (P >0.05, Fisher's exact test). No significant immunohistochemical reactions with iNOS, MIB-1 or p53 protein were observed in normal brain tissue sections. We conclude that primary brain tumors express iNOS, and that iNOS expression in brain tumor cells may depend, in part, on cellular proliferation potential. Based on the fact that SOD1 scavenges oxidative-stress species originating from large amounts of nitric oxide (NO) produced by iNOS, iNOS-expressing brain tumor cells may protect themselves against NO cytotoxicity by overinducing SOD1.

Blotting, Western↗
PubMed2002

Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation.

Recent studies have documented carbonyl stress involvement in the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS). The aim of the present study was to assess a role for carbonyl stress in motor neuron degeneration associated with superoxide dismutase-1 (SOD1) mutant familial ALS and its transgenic mouse model, using an immunohistochemical investigation of advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs). In the spinal cords from six familial ALS patients with SOD1 A4V mutation and six transgenic mice expressing G93A mutant human SOD1, immunoreactivities for N(epsilon)-(carboxyethyl)lysine, argpyrimidine, pyrraline and N(epsilon)-(carboxymethyl)lysine as AGEs were distinct in almost all of the reactive astrocytes and obscure in the residual neurons, whereas no immunoreactivity for pentosidine as an AGE, or 4-hydroxy-2-nonenal-histidine, malondialdehyde-lysine or acrolein-lysine as ALEs was detectable. Spinal cords from age-matched control humans and mice exhibited no significant immunoreactivities for the examined products. Our results indicate that protein glycation, but not lipid peroxidation, is enhanced in ALS patients with an SOD1 mutation and mutant SOD1 transgenic mice, in which certain AGEs are selectively formed in the spinal cord astrocytes.

Adult↗
PubMed2002

Monoclonal antibody to stage-specific fetal brain 68-kDa glycoprotein (FGP68) revealed increased FGP68 expression in human primary brain tumors.

We have produced a novel rat IgG(2a) monoclonal antibody against a stage-specific fetal brain glycoprotein of 68 kDa (FGP68), and succeeded in applying it to staining paraffin sections. To gain some insight into the pathobiological significance of this FGP68, this monoclonal antibody was used in immunohistochemical studies to compare the expression of FGP68 and Ki-67 antigen (MIB-1) in 235 primary brain tumors. Approximately half of the glioblastomas multiforme (GBMs) (44/75) and anaplastic astrocytomas (9/17) as well as some astrocytomas (5/30), medulloblastomas (2/14) and primitive neuroectodermal tumors (2/10) had tumor cells that expressed FGP68; however, pilocytic astrocytomas (0/7), oligodendrogliomas (0/15), ependymomas (0/6), schwannomas (0/21), meningiomas (0/22) and pituitary adenomas (0/18) did not express FGP68. The values of the MIB-1 labeling index were statistically higher in GBMs (0.005< P<0.01, Wilcoxon rank-sum test) and anaplastic astrocytomas (0.025< P<0.05) that expressed FGP68 than in those that did not. Normal brain tissue from 20 individuals aged 3-75 years was negative for FGP68 and MIB-1. We conclude that primary brain tumors express FGP68, one of the oncofetal proteins derived from fetal brain, and that FGP68 expression in certain brain tumor cells may depend, in part, on proliferation potential. Based on the possibility that the stage-specific FGP68 plays an important role in brain embryogenesis, some of FGP68-expressing tumor cells might phylogenetically revert to more primitive cells.

Animals↗
PubMed2002

Two cases of spinal meningeal melanocytoma.

Meningeal melanocytoma is a rare pigmented tumor originating from the melanocytes that generally occurs in the posterior fossa and the spinal cord. Although it is known as a relatively benign tumor, some recurrences have been reported. We report two cases of spinal meningeal melanocytoma with immunohistochemical and ultrastructural studies. In addition, we include a summary of published cases since the first case of Limas and Tio in 1972.

Adult↗