Search PubMed⌕ Search

Biomedical subjects

S Yagishita

Publications and source records attributed to S Yagishita.

At least 19 recordsLinked to original sources
PubMed2001

Intracellular processing of aggregated tau differs between corticobasal degeneration and progressive supranuclear palsy.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are sporadic neurodegenerative diseases with intracytoplasmic aggregates of the microtubule-associated protein, tau, in neurons and glial cells. Immunoblot analysis of detergent-insoluble brain extracts of patients with CBD and PSP shows distinctive patterns of tau fragments. These results suggest differing intracellular processing of aggregated tau in these two diseases despite an identical composition of tau isoforms. Such biochemical differences may be related to the neuropathological features of these diseases.

Aged↗
PubMed2001

Spinal tanycytic ependymomas.

Three cases of spinal tanycytic ependymoma are reported, a man aged 45 years and two women aged 36 and 55 years. Each patient developed gradual paraparesis over a few months prior to admission. Magnetic resonance imaging showed an enhancing, well-circumscribed tumor in the spinal cord in each case. Histologically, the tumors consisted of monotonous proliferation of long spindle cells with markedly eosinophilic cell processes; focally forming perivascular pseudorosettes. The tumor cells were strongly immunopositive for glial fibrillary acidic protein, S-100 protein and vimentin. Ultrastructurally, in addition to massive intermediate filaments, many tumor cells showed abundant microtubules. Well-developed desmosomes and microvilli/cilia-lined microlumina were occasionally observed. The tumors were grossly totally removed and the patients remain recurrence free at 9, 9, and 2 years postoperatively. Reviewing reported cases including our three cases, tanycytic ependymoma may occur frequently in spinal cord, especially in the cervical region of the spinal cord. Since histologically it resembles pilocytic astrocytoma and schwannoma, tanycytic ependymoma should be included in the differential diagnosis of benign spindle cell tumors of the central nervous system.

Adult↗
PubMed2001

Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick's disease, corticobasal degeneration and progressive supranuclear palsy.

We investigated isoform composition of aggregated tau protein in brains with Pick's disease (PiD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) by immunoblot analysis of sarkosyl-insoluble fractions of brain homogenates. We also examined the adjacent brain tissues immunohistochemically with a rabbit antibody, Ex10, which specifically recognizes exon 10 of tau. The Ex10 recognizes tau isoforms with four microtubule-binding repeats (4Rtau) but not those with three microtubule-binding repeats (3Rtau). Sarkosyl-insoluble tau from the brains of patients with CBD and PSP consisted of 4Rtau. Insoluble tau from the PiD brains contained both 3Rtau and 4Rtau, where 3Rtau predominated over 4Rtau. In brain tissues of CBD and PSP, Ex10 immunostained all neuronal and glial tau-positive structures. They included pre-tangles, astrocytic plaques, tuft-shaped astrocytes, and oligodendroglial coiled bodies. In PiD brains, astrocytic inclusions were also positive for 4Rtau. However, the majority of, if not all, Pick bodies and oligodendroglial tau inclusions were negative for 4Rtau. Such results suggest that, in neurons and oligodendroglia, tau isoforms involved in the pathological processes differ between CBD/PSP and PiD, and are thus disease specific. This contrasts with the astrocytic tau isoforms that accumulate similarly in all three disorders.

Astrocytes↗
PubMed2001

Non-expanded polyglutamine proteins in intranuclear inclusions of hereditary ataxias--triple-labeling immunofluorescence study.

Neuronal intranuclear inclusions (NIIs) found in CAG/polyglutamine-expansion disorders contain both expanded polyglutamine and the gene product without the CAG repeat. The gene product containing expanded polyglutamine has, therefore, been considered to be a major component of NIIs. In this immunohistochemical study, we showed recruitment of ataxin-2, ataxin-3 and TATA box binding protein (TBP) into NIIs of the pontine neurons of spinocerebellar ataxia type (SCA) 1, SCA2, SCA3 and dentatorubral-pallidoluysian atrophy brains. Triple-labeling immunofluorescence demonstrated colocalization of ataxin-2 and ataxin-3 in NIIs containing expanded polyglutamine, irrespective of the disease examined. These in vivo findings indicate that polyglutamine proteins recruited into NIIs are not restricted to their expanded form. Among these proteins, recruitment of ataxin-2 was least frequent in every case examined, suggesting that the rate of recruitment partly depends on the protein transported into NIIs. Because other proteins lacking polyglutamine motif were not detected in NIIs, it is suggested that the presence of polyglutamine is a prerequisite for these proteins to be recruited into nucleus and to form NIIs. Interaction between expanded and non-expanded polyglutamine may play roles during these processes.

Ataxin-3↗
PubMed2001

Distribution of cerebral cortical lesions in Pick's disease with Pick bodies: a clinicopathological study of six autopsy cases showing unusual clinical presentations.

We investigated six Japanese autopsy cases of Pick's disease with Pick bodies (PDPB) both clinically and pathologically, and examined the distribution of their cerebral cortical lesions using hemisphere and/or bisphere specimens. The lesions were classified into three categories (slight, moderate, and severe). Two patients with a clinical diagnosis of primary progressive apraxia and of slowly progressive aphasia had speech apraxia as their initial signs, and the other two patients were suspected as having Alzheimer's disease, with the clinical diagnosis of the remainder two patients being presenile dementia and depression, respectively. Extrapyramidal signs, believed to be rare in PDPB, were present in four patients. Severe lesions were multicentrically present in the cerebral cortices of all six cases. In two patients with speech apraxia, severe lesions were seen in the primary motor area, which generally has not been regarded as an "atrophic center" in Pick's disease. Furthermore, in a patient with depression, severe lesions were more widespread in the convexity than in the orbital region of the frontal lobe. The parietal lobes, including the postcentral gyrus usually believed to be spared in Pick's disease, were severely involved in three patients. We postulate that the clinical features of PDPB have a much wider spectrum than previously believed. In addition, we believe that the distribution of the cerebral cortical lesions in PDPB is more widespread than previously assumed, and that clinical manifestations of PDPB depend to some extent on the topographic distribution of the cerebral cortical lesions.

Aged↗
PubMed2001

Distribution and dynamic process of neuronal cytoplasmic inclusion (NCI) in MSA: correlation of the density of NCI and the degree of involvement of the pontine nuclei.

MSA is a sporadic degenerative disease that occurs in striatonigral degeneration (SND), SDS and most cases of sporadic OPCA. Oligodendroglial inclusion is a hallmark of MSA. Recently there have been a small number of reports of neuronal argyrophilic inclusions. To clarify the distribution and dynamic process of neuronal cytoplasmic inclusions (NCI), 31 cases of MSA were studied using histology, immunohistochemistry, and electron microscopy. The inclusions were exclusively found in the pontine nucleus and there was a correlation between the incidence of NCI and the severity of OPCA, but not of SND. NCI were increased to some extent in the cases with moderate OPCA and decreased in number in proportion to devastation of the pontine nuclei. Immunohistochemical and ultrastructural features of NCI were virtually identical to those of glial cytoplasmic inclusions (GCI), which gives some clues to the pathogenesis of MSA. It is tempting to interpret this as NCI playing a significant role in the degenerative changes of the neurons at least in the pons. Further systematic studies on NCI in the other brain regions are necessary to elucidate the pathogenesis of neuronal degeneration in MSA.

Adult↗
PubMed2000

Asymmetrical temporal lobe atrophy with massive neuronal inclusions in multiple system atrophy.

This report concerns a rare association of asymmetrical temporal lobe atrophy with multiple system atrophy (MSA). A 53-year-old Japanese woman developed cerebellar ataxia and parkinsonism and was diagnosed as olivopontocerebellar atrophy (OPCA). This patient showed forgetfulness and subsequent disorientation even in the early stage of the disease. She fell into a decorticate state at the age of 64, and died a year later. The autopsy showed MSA with asymmetrical atrophy of temporal lobes, intraneuronal globular inclusions mostly confined to the hippocampus, amygdaloid nucleus, and most abundant in the granule cells in the dentate fascia. These inclusions were intensely argyrophilic and expressed marked immunoreactivity to ubiquitin, but not to neurofilament (NF), tau and paired helical filaments (PHF). Ultrastructurally, they were composed of scattered short filamentous structures of 15 to 30 nm in diameter, ribosome-like granules, mitochondria and lipofuscin. The lack of immunoreactivity against tau, NF and PHF suggests that the inclusions are distinct from Pick bodies. To our knowledge, MSA in association with asymmetrical temporal lobe atrophy with the present neuronal inclusions has not been reported. This case is distinct from MSA combined with atypical Pick's disease in the distribution and immunohistochemical properties of neuronal inclusions, and may present a new variant of MSA since the neuronal inclusions are similar, in many respects, to those of neuronal inclusions reported in MSA. Globular inclusions are also discussed in variants of Pick's disease, amyotrophic lateral sclerosis and Alzheimer's disease.

Atrophy↗
PubMed2000

Ataxin-3 is translocated into the nucleus for the formation of intranuclear inclusions in normal and Machado-Joseph disease brains.

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is one of the dominantly inherited cerebellar ataxias. The gene responsible for the disease, a novel gene of unknown function, encodes ataxin-3 containing a polyglutamine stretch. Although it has been known that ataxin-3 is incorporated into neuronal intranuclear inclusions (NIIs) in neurons of affected regions, the relationship between NII formation and neuronal degeneration still remains uncertain. In the present study we show two different conditions in which ataxin-3 is recruited into the nucleus and suggest a process to form nuclear inclusions. In normal brains, wild-type ataxin-3 localizes within the ubiquitin-positive nuclear inclusion, the Marinesco body, indicating that ataxin-3 is recruited into the nuclear inclusion even in the absence of pathologically expanded polyglutamine. In MJD/SCA3 brains, immunohistochemical analyses with anti-ataxin-3 antibody, anti-ubiquitin antibody, and monoclonal antibody 1C2 known to recognize expanded polyglutamine revealed differences in frequency and in diameter among NIIs recognized by each antibody. These results were confirmed in the same inclusions by double immunofluorescent staining, suggesting that expanded ataxin-3 forms a core, thereby recruiting wild-type ataxin-3 into the nucleus around the core portion, and then followed by activation of the ubiquitin/ATP-dependent pathway. Recruitment of ataxin-3 into the nucleus and formation of nuclear inclusion under two different conditions suggest that ataxin-3 may be translocated into the nucleus under certain conditions stressful on neuronal cells such as aging and polyglutamine neurotoxicity.

Ataxin-3↗
PubMed2000

An autopsy case of atypical adrenoleukomyeloneuropathy in childhood.

Adrenoleukomyeloneuropathy (ALMN) usually occurs in adulthood, it being extremely rare in childhood. We reported a quite atypical clinical case of ALMN as a variant of adrenoleukodystrophy (ALD). The onset was at 5 years 7 months and ataxia was the major symptom. His condition progressed rapidly to a vegetative state within 1 year. At the age of 11 years and 11 months he died of pneumonia and an autopsy was performed. We herein reported the neuropathological findings in this rare case. The autopsy revealed marked atrophy with diffuse demyelination and astrogliosis throughout the cerebrum, cerebellum and brainstem. Massive degeneration of the pyramidal tracts and loss of neurons were also seen in the spinal cord. The adrenal cortex showed marked atrophy with a striated cytoplasm in ballooned cells. These findings include pathological characteristics of both ALD and adrenomyeloneuropathy (AMN), suggesting ALMN. However, diffuse demyelination with gliosis in the cerebrum and cerebellum is quite atypical for ALMN. They might explain his atypical clinical course, especially the early onset of the disease with ataxia and rapid deterioration.

Adrenoleukodystrophy↗
PubMed2000

Vascular structure of arteriovenous malformations.

Cerebral arteriovenous malformations (AVMs) are classified angiographically into two types: the arteriovenous fistula (AVF) type and the plexiform type. However, the differences in vascular structure of these two types have not been clarified. The purpose of the present study is to elucidate the vascular structure of plexiform AVMs and to discuss the clinical significance of this classification of AVMs. Specimens of AVMs resected in 8 cases and identified by cerebral angiography as plexiform AVMs were examined. Immediately after their removal, microdissection of the terminal arterial feeder, the nidus, and the venous drainer was performed under a microscope. A histological examination of each element was then conducted. Microdissection of a portion of the vascular mass that formed the nidus made it possible to separate individual vessels of the mass from each other. Many of these individual vessels connected with the feeder on one side, while the other side anastomosed with the drainer, thus exhibiting the morphology of an AVF. From our examination of the AVMs in the present study, we inferred that the plexiform type is fundamentally a conglomeration of AVFs. It is therefore suggested that the vascular structure of this type of AVM is not fundamentally different from that of the AVF type.

Adult↗
PubMed2000

[Intrathecal 2% tetracaine causes mild histological lesions in the spinal cord without detectable sensory deficits on paw stimulation test in rats].

The purpose of this study is to determine if intrathecal 2% tetracaine (TC) causes histological changes by its neurotoxicity, and to examine the relationship between the lesions and neurological functions. Twenty-two rats received either 2% TC or 0% TC dissolved in 10% glucose, via an intrathecal catheter terminated at T 13 level. Neurological deficits were evaluated by rat's behavior and paw stimulation test (UCSF). Five days after drug administration, the L 1 spinal cord with the anterior and posterior roots and cauda equina were excised for light and electron microscopy. Four rats out of 8 in 2% TC group showed mild pathological changes induced by neurotoxicity mainly in the posterior roots and slightly in the posterior column. However, there were no significant differences in sensory and behavioral function between the rats who had received 2% TC with lesion and the others with no lesion. As many rootlets enter one segment of the spinal cord, mild and restricted lesions may be difficult to detect by sensory tests. These findings may explain the fact that the patients with transient neurologic symptoms (TNS) are normal by neurological tests.

Anesthesia, Spinal↗
PubMed1999

Neuronal intranuclear inclusions in spinocerebellar ataxia type 2: triple-labeling immunofluorescent study.

Spinocerebellar ataxia type 2 (SCA2) is associated with an expansion of CAG/polyglutamine-repeat of a gene of unknown function. We performed an immunohistochemical study to identify the immunolocalization of the disease protein ataxin-2 in normal and SCA2 patients. Although normal and expanded ataxin-2 were ubiquitously localized to the cytoplasm of neurons, ubiquitinated intranuclear inclusions were observed selectively in 1-2% of neurons of affected brain regions except the cerebellum. Triple-labeling immunofluorescence revealed that ataxin-2, expanded polyglutamine and ubiquitin were colocalized to these neuronal intranuclear inclusions (NIs), indicating that SCA2 shares morphological characteristics common to other neurological disorders associated with an expansion of CAG/polyglutamine-repeat. Lack of NIs in the cerebellar lesion, however, suggests the discrepancy between formation of NIs and neuronal degeneration in SCA2.

Ataxins↗
PubMed1999

Cerebellar clear cell ependymoma mimicking hemangioblastoma: its clinical and pathological features.

BACKGROUND: As the clinical and pathological significance of cerebellar clear cell ependymoma (CCE) has not been recognized in the past, eight cases of cerebellar CCEs were studied. METHODS: Subjects were six men and two women, and their ages ranged from 23 to 64 years old. Their neuroradiological, operative, and pathological features were reviewed. RESULTS: The tumors frequently showed high vascularity on angiography and marked enhancement on computerized tomography. Grossly, six tumors exhibited a "cyst with mural nodule" and two were mostly solid containing small cysts. At operation, the tumor nodules were dark red in color and the cysts contained xanthochromic fluid. Microscopically, all tumors displayed mostly clear round cells and abundant blood vessels. Although they commonly lacked the characteristic features of ependymomas, immunostaining and electron microscopy confirmed their ependymal origin. CONCLUSIONS: The results indicate that cerebellar CCEs closely mimic hemangioblastoma both clinically and pathologically, which suggests CCE should be considered in the differential diagnosis of vascular tumors of the cerebellum. Some diagnostic clues to differentiate CCE from hemangioblastoma are discussed.

Adult↗
PubMed1999

Autosomal dominant spinocerebellar degenerations. Clinical, pathological, and genetic correlations.

Historical review on hereditary spinocerebellar degenerations (SCD) revealed that some CAG repeat diseases were formerly diagnosed under several different names because of their clinical and pathological heterogeneity. A genetic abnormality in these hereditary SCDs (often with expanded CAG repeat) corresponds to a definite prototypic combination of the principal lesions in the cerebellar, extrapyramidal, and oculomotor systems, which allows neuropathological differentiation between these entities. Variability of both clinical and pathological features is mainly related to the patient's age at onset, which is often correlated with the number of CAG repeat size. Several characteristics are suggestive of these SCD: preferential degeneration of specific systems, size reduction at cellular or tissue level not accompanied by glial reaction (simple atrophy or hypoplastic change) and presence of recently identified ubiquitin positive inclusions in neurons are characteristics of these SCDs. These features provide further insight into the phenotypic development of a genetic abnormality.

Atrophy↗
PubMed1998

Regional quantitative analysis of tau-positive neurons in progressive supranuclear palsy: comparison with Alzheimer's disease.

In patients with progressive supranuclear palsy (PSP), various tau-positive abnormal structures are found in the cerebral cortex as well as in the subcortical nuclei. Similar tau-positive abnormalities are also identified in cortico-basal degeneration (CBD). It is therefore questionable as to whether PSP can be neuropathologically differentiated from CBD. It also remains nuclear whether neurofibrillary tangles (NFT) in the cerebral cortex of PSP patients consist of PSP-NFT or concomitant Alzheimer's disease (AD)-NFT, although there have been some reports suggesting that PSP- and AD-NFT are different with respect to distribution pattern and biochemical character. In this study, a regional quantitative analysis of the distribution and antigenicity of tau-positive neurons (TPN) was performed in PSP cases and compared with that in AD cases. TPN consisted of NFT with tangle-formation and pretangle neurons (PN) without tangle-formation. In addition, NFT were subdivided into mature and immature NFT according to the difference of staining properties with anti-tau-related antibodies. The comparison of the TPN of the PSP cases with those of the AD cases revealed that the degree of tangle-formation in the TPN of AD was similar in all of the examined regions, while that in the TPN of PSP varied according to the region and case. Moreover, the NFT in the PSP and AD cases had different distributions according to the cortical layer and subnucleus, even in the common predilection sites of PSP and AD, suggesting that NFT in these regions of the PSP cases consist mainly of PSP-NFT. In addition, the PSP cases could be divided into two groups according to the difference of the tangle-formation of TPN; group I with typical PSP pathology and group II with atypical PSP pathology similar to CBD. This suggests that there is a continuity between PSP and CBD with respect to the distribution and antigenicity of TPN.

Aged↗
PubMed1998

Loss of the dentate nucleus neurons is associated with torpedo formation: a morphometric study in progressive supranuclear palsy and dentatorubro-pallidoluysian atrophy.

Cerebellar torpedoes can be induced by direct damage to Purkinje cell axons. This raises the possibility that the loss of dentate nucleus neurons (DNNs) may also cause torpedo formation through synaptic detachment between DNNs and Purkinje cell axon terminals. To investigate this possibility, we conducted a morphometric study with an image analyzer in progressive supranuclear palsy (PSP) and dentatorubro-pallidoluysian atrophy (DRPLA). Using horizontal and sagittal sections of the cerebellar hemispheres containing the greatest proportion of the dentate nucleus, we determined the line densities of torpedoes, Purkinje cells, and DNNs. In PSP and DRPLA, the densities of DNNs were significantly lower, and the densities of torpedoes much greater than in controls, while those of Purkinje cells were normal in both diseases. In addition, the torpedo densities in PSP and DRPLA showed a strong negative correlation with the DNN densities. Thus, this study clearly demonstrated that torpedoes are formed in association with the loss of DNNs, suggesting that they may occur in consequence of synaptic disconnection of Purkinje cells from DNNs.

Adult↗
PubMed1998

Scanning electron microscopical study of neurofibrillary tangles in a presenile patient with Down's syndrome.

An autopsy case of a 64-year old woman with Down's syndrome (DS) is reported with a special reference to the ultrastructure of neurofibrillary tangles (NFTs). NFTs and senile plaques were diffusely observed throughout the brain. The most severe changes were seen in the amygdaloid nuclear complex and hippocampus. Immunohistochemistry of the NFTs and senile plaques indicated the features identical to those in Alzheimer's disease (AD). Ultrastructurally, NFTs were composed of straight filaments and two profiles of paired helical filaments (PHFs). By transmission electron microscopy, straight filaments measured 25-28 nm in diameter. As to the PHFs, one type was 33 nm in maximum diameter and constricted at a 75- to 80-nm interval. The other was 16-18 nm in maximum diameter and constricted at a 35- to 40-nm interval. By scanning electron microscopy, the diameter of the straight filaments measured up to 28-30 nm. Two profiles of PHFs were observed. One type of PHF showed thick filaments about 34 nm in maximum diameter and constrictions at an 80-nm interval. The other was about 17 nm in diameter and constricted at a 40-nm interval. The helical directions of both PHFs were left-handed. The frequency of PHFs with short interval was much higher in DS than AD. Furthermore, the length of the periodicity of this type of PHF was somewhat less than that of AD. Thus, these findings suggest that the neuropathological changes in DS and AD share a common etiopathology, but that some differences in the PHFs between DS and AD may reflect on molecular difference in the proteins or peptides associated with PHF formation.

Alzheimer Disease↗