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Saburo Yagishita

Publications and source records attributed to Saburo Yagishita.

17 recordsLinked to original sources
PubMed2006

Intranuclear immunolocalization of 14-3-3 protein isoforms in brains with spinocerebellar ataxia type 1.

Immunolocalization of 14-3-3 protein isoforms, one of the interacters with ataxin 1, was investigated in spinocerebellar ataxia type 1 (SCA 1) brains using isoform-specific antibodies. Samples from the pons and from the cerebellum of four SCA1 cases and three controls were studied. The intensity of the immunoreactivity (IR) and its subcellular topography were analyzed. In control subjects, granular immunoreactivity for an epitope common to all known isoforms of 14-3-3 proteins (14-3-3 COM) found in the cytoplasm of some pontine and dentate nucleus neurons was weak. It was observed in some Purkinje cells, while its intensity varied. Many nuclei of those neurons and Purkinje cells of SCA1 were intensely immunopositive for 14-3-3 COM, while it was less in their cytoplasm. Expanded polyglutamine epitope was colocalized to 14-3-3 COM epitope in some pontine neurons, sometimes accumulated in intranuclear inclusion-like structures. This findings support previous reports that 14-3-3 proteins stabilize mutant ataxin 1 in nucleus and possibly lead to neurodegeneration. However, nuclear localization of 14-3-3 proteins in SCA1 brains was dependent on its isoforms, i.e. pontine neurons intensely positive for beta, Purkinje cells for tau and dentate nucleus neurons for both, while all of those neurons were consistently positive for zeta isoform, although sigma isoform tended to be located in the cytoplasm. Nuclear accumulation and isoform- and region-dependent subcellular localizations of 14-3-3 proteins may be related to SCA1 pathology, which exhibits marked regional variability.

14-3-3 Proteins↗
PubMed2006

Pathological heterogeneity of the precentral gyrus in Pick's disease: a study of 16 autopsy cases.

This report concerns the upper motor neuron involvement in 16 autopsy cases of Pick disease with Pick bodies, including 11 cases reported by us previously. Prominent, circumscribed atrophy of the precentral gyrus, conspicuously in the lower portion, was noted in one case. Loss of Betz cells and astrocytosis of the precentral gyrus layer V were encountered in 15 cases (94%) and eight cases (50%), respectively. Appearance of Pick bodies and ballooned neurons in the precentral gyrus layer V was confirmed in seven cases (44%). Degeneration of the pyramidal tract in the medulla oblongata was noted in all 15 cases in which this structure was examined. Pyramidal signs were observed in four (67%) of the six cases that were neurologically sufficiently examined: hyperreflexia in four cases (67%), spasticity in one case (17%). Babinski sign was not encountered in any of the six cases. In all four cases having pyramidal signs, degeneration of the pyramidal tract was observed. In contrast, two cases having degeneration of the pyramidal tract did not develop pyramidal signs. In Pick's disease with Pick bodies, obvious involvement of the precentral gyrus and pyramidal tract was not previously noticed. Furthermore, we suggest that pyramidal signs in Pick's disease with Pick bodies have been underestimated.

Aged↗
PubMed2006

Autopsy case of Creutzfeldt-Jakob disease with Met/Val heterozygosity at codon 129 and type 1 protease-resistant prion protein presenting some florid-type plaques and many Kuru plaques in the cerebellum.

We report an atypical case of CJD. The clinical course was similar to a classic CJD phenotype, but histopathological study revealed several florid-type plaques in the amygdale and abundant Kuru plaques in the cerebellum that are atypical of classic CJD. Molecular analysis showed methionine/valine heterozygosity at codon 129 and no pathogenic mutation in the coding region of the prion protein gene. Western immunoblots revealed type 1 protease-resistant prion protein (PrPres), and a ration analysis of PrPres showed a high ratio of the diglycosylated form and a low ratio of the non-glycosylated form. Our case could not be precisely classified in any of Parchi's six variants. It suggests the existence of some factors that determine the phenotypic variability other than the codon 129 genotypes in the PrP gene or the physicochemical properties of PrPres.

Autopsy↗
PubMed2006

Endodermal cyst ventral to the lower brain stem.

A 28-year-old woman presented with a rare case of endodermal cyst located ventral to the lower brain stem manifesting as recurrent aseptic meningitis. Computed tomography and magnetic resonance imaging demonstrated a cystic mass located ventral to the lower brain stem and extending from the prepontine to the upper cervical (C-2) cistern. The lesion was totally removed through a retrosigmoid craniotomy and C1-2 hemilaminectomy. Histological and immunohistochemical examination showed the cyst was derived from the endoderm. The histological diagnosis was endodermal cyst. Early diagnosis and surgical removal are important for patients with these cysts.

Adult↗
PubMed2004

Silver stains distinguish tau-positive structures in corticobasal degeneration/progressive supranuclear palsy and in Alzheimer's disease--comparison between Gallyas and Campbell-Switzer methods.

Possible differences in silver-staining profiles and their relation to tau-like immunoreactivity were investigated on cortical sections from corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Down's syndrome (DS) and Alzheimer's disease (AD). Pairs of mirror sections were double-fluorolabeled with an anti-PHF tau (AT8) antibody and thiazin red (TR), a fluorochrome that labels fibrillary structures such as neurofibrillary tangles (NFTs). Subsequently, one of the pair was stained with Gallyas method (GAL), and the other with Campbell-Switzer method (CS). Identification of the same structure on the corresponding microscopic fields enabled a comparison of four different profiles of each structure: AT8 immunoreactivity, and affinity to TR, GAL and CS. NFTs of DS/AD, containing three- and four-repeat tau, were positive for TR, GAL and CS. AT8-immunoreactive structures of CBD/PSP, containing mainly four-repeat tau, were positive for GAL, but negative for CS and TR. This discrepancy is explainable if the argyrophilia with GAL is related to deposits containing four-repeat tau, while that with CS is linked to those containing three-repeat tau. The lack of CS labeling may also be related to poor TR staining, possibly representing scarcity of fibrillary structure in CBD/PSP. The absence of CS staining is characteristic of tau-positive structures of CBD/PSP, which is readily distinguishable from NFTs of DS/AD, hence is of potential pathological and diagnostic relevance.

Aged↗
PubMed2004

Was the ataxia of Pierre Marie Machado-Joseph disease?: A reappraisal based on the last autopsy case from la Salpêtrière Hospital.

Nosological placement of l'hérédo-ataxie cérébelleuse de Pierre Marie (HAC) has never been established even after several autopsy cases from the original Haudebourg family had been reported. To reappraise the clinical and pathological features of HAC in the current framework of hereditary ataxias, we screened the autopsy records of la Salpêtrière hospital and identified a patient with a diagnosis of HAC who underwent an autopsy in 1943. Clinical features included heredity compatible with autosomal dominant inheritance, spasticity, increased tendon reflexes, mask-like face, visual impairment, nuclear ophthalmoparesis, and exophthalmos in addition to progressive ataxia. Pathological lesions included the spinal cord (spinocerebellar tracts, anterolateral fascicles, and posterior column), cerebellar dentate nucleus, pontine nucleus, pallidum, motor neurons including the oculomotor nucleus, and substantia nigra. The cerebellar cortex and inferior olives were preserved. These clinical and pathological features, similar to those described in patients from the Haudebourg family, a core prototype of HAC, are indistinguishable from those of Machado-Joseph disease. It would then be possible to conclude that some of the patients historically considered to have HAC would today be classified as having Machado-Joseph disease.

Adult↗
PubMed2004

Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative diseases that are characterized by intracytoplasmic aggregates of hyperphosphorylated tau with four microtubule-binding repeats. Although PSP and CBD have distinctive pathological features, no biochemical difference in aggregated tau has been identified. In this study, we examined the brains of eight patients with PSP, six patients with CBD, and one atypical case with pathological features of both CBD and PSP. On immunoblots of sarkosyl-insoluble brain extracts, a 33kDa band predominated in the low molecular weight tau fragments in PSP, whereas two closely related bands of approximately 37kDa predominated in CBD. Immunoblots of the atypical case showed both the 33kDa band and the 37kDa doublet. Protein sequencing and immunochemical analyses showed that the 33kDa band and the 37kDa doublet consisted of the carboxyl half of tau with different amino termini. These results suggest that, despite the identical composition of tau isoforms, different proteolytic processing of abnormal tau takes place in these two diseases. Such a biochemical divergence may be related to the neuropathological features of these diseases.

Aged↗
PubMed2004

Coexistence of CJD and Alzheimer's disease: an autopsy case showing typical clinical features of CJD.

The present report concerns an autopsy case of CJD showing typical clinical features of CJD. The patient was a Japanese woman without hereditary burden or dementing disorder anamnesis who was 70-years-old at the time of death. She developed gait disturbance at age 68, followed by memory impairment, visual disturbance, and myoclonus. A neurological examination approximately 2 months after the disease onset revealed akinetic mutism, in addition to periodic synchronous discharges on electroencephalogram. Serial neuroradiological examinations disclosed progressive atrophy of the brain. She died of bronchopneumonia 25 months after the disease onset. The brain weighed 560 g (cerebrum 490 g, brainstem with cerebellum 70 g). Macroscopically, neuropathological examination showed prominent atrophy of the cerebrum, caudate nucleus, and cerebellum, in addition to necrosis of the cerebral white matter, compatible with panencephalopathic CJD. Histologically, there was neuronal loss with or without spongiform change in the cerebral cortex, parahippocampal gyrus, amygdala, striatum, pallidum, thalamus, pontine nucleus, and cerebellar granule cells, in addition to diffuse synaptic-type prion staining in the cerebrum and cerebellum. Furthermore, senile plaques, compatible with definite Consortium to establish a registry for Alzheimer's disease rank Alzheimer's disease, and neurofibrillary changes of the limbic system, consistent with stage IV of Braak's classification, were found. Based on these clinicopathological findings and a review of the published literature, it is concluded that there were two forms of coexistence of CJD and Alzheimer's disease in the same patient.

Aged↗
PubMed2003

Reversible conformational change of tau2 epitope on exposure to detergent in glial cytoplasmic inclusions of multiple system atrophy.

Tau-like immunoreactivity (IR) on glial cytoplasmic inclusions (GCIs) of multiple system atrophy (MSA) was investigated with a panel of anti-tau antibodies and we found that tau2, one of the phosphorylation-independent antibodies, preferentially immunolabeled GCIs. Co-presence (0.03%) of polyethyleneglycol- p-isooctylphenyl ether (Triton X-100, TX) with tau2, however, abolished this IR on GCIs, but did not abolish tau2 IR on neurofibrillary tangles (NFTs). Tau2-immunoreactive bands on immunoblot of brain homogenates from MSA brains were retrieved mainly in a TRIS-saline-soluble fraction, as reported in normal brains. This was in contrast to SDS-soluble fractions from brain with Down's syndrome, which contained tau2-immunoreactive bands of higher molecular weight. It indicates that the appearance of tau2 IR on GCIs is not related to hyperphosphorylation of tau. These tau2-immunoreactive bands, except those from bovine brain, were similarly abolished in the presence of TX (0.06%), and repeated washing after exposure to TX restored the tau2 IR on immunohistochemistry and on immunoblot. These findings can be explained if the modified tau2 epitope undergoes a reversible conformational change on exposure to TX, which is reversible after washing. Because the conformation centered at Ser101 of bovine tau is crucial for its affinity to tau2, the Ser-like conformation mimicked by its human counterpart Pro may represent pathological modification of tau shared by GCIs and NFTs. The relative resistance of tau2 epitope on NFTs on exposure to TX suggests that tau woven into NFTs confers additional stability to the pathological conformation of tau2 epitope. The conformation of the tau2 epitope in GCIs is not as stable as in NFTs, suggesting that tau proteins are not the principal constituents of the fibrillary structures of GCIs, even though they were immunodecorated with tau2. The difference in the susceptibility of the tau2 epitope to TX may distinguish its conformational states, which are variously represented according to disease conditions.

Aged↗
PubMed2003

Different immunoreactivities of the microtubule-binding region of tau and its molecular basis in brains from patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration.

The microtubule-associated protein tau accumulates as cytoplasmic inclusions in Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We investigated the immunoreactivity of tau-positive structures using a panel of antibodies to epitopes spanning the entire length of the tau molecule. In ethanol-fixed brain tissues, most antibodies to the microtubule-binding domain (MBD) required formic acid (FA) treatment to stain tau inclusions in PSP and CBD. This is in contrast with the intense labeling of neurofibrillary tangles in AD without FA treatment. Pick bodies (PiB) in PiD showed an intermediate pattern with respect to the immunoreactivity of the MBD because accumulated tau in PiB mostly lacks the insertion of exon 10, and the proportion of tau phosphorylated at Ser262 is smaller than in other abnormal tau structures. Such immunohistochemical profiles appeared to correlate with the occurrence of the smeared tau on immunoblot analysis of brain homogenate. The smeared tau was more abundant in AD and PiD than in PSP and CBD. Since the smeared tau was N-terminally truncated and was characteristic of advanced forms of modified tau, these findings suggest that tau accumulated in AD and PiD was processed more markedly than that in PSP and CBD. The MBD of tau may be masked in the presence of the intact N terminus and require FA treatment for antibody recognition in tissue sections. Advanced modification may expose the MBD in brain tissues of AD and PiD. It is suggested that the processing of abnormally accumulated tau characterizes the pathophysiology of each tauopathy.

Aged↗
PubMed2003

Pineal parenchymal tumor with marked retinoblastic differentiation: case report.

A 53-year-old woman was found to have a tumor in the pineal region. Histologically, Homer-Wright rosettes were sporadically distributed in a diffuse proliferation of round tumor cells that were immunoreactive for synaptophysin and chromogranin. A few perivascular pseudorosettes were also present, and the perivascular tumor cells were immunoreactive for glial fibrillary acidic protein and vimentin. By electron microscopy, well-developed junctions and pronounced interdigitation of abutting plasma membranes were noted in many tumor cells, as well as abundant intracytoplasmic microtubules. These findings indicated that the tumor was a pineal parenchymal tumor accompanied by an extraordinary epithelial-like differentiation, suggesting retinoblastic photoreceptor cell differentiation.

Brain Neoplasms↗
PubMed2003

Dissecting aneurysm of the intracranial vertebral artery associated with proximal focal degeneration of the elastica: a comparative pathological study of the vertebral artery in patients with and without aneurysms.

BACKGROUND: The pathogenesis underlying intracranial dissecting aneurysms remains unclear. We performed a detailed study using vertebral artery specimens obtained at autopsy from patients with and without aneurysms to identify the primary abnormality resulting in weakness of the elastica. We compared our observations with those made in specimens manifesting the normal atherosclerotic process. METHODS: Using histologic methods, we examined intracranial vertebral artery specimens from two autopsied aneurysm patients and 13 autopsied control cases to compare the state of atherosclerosis and the weakness of the elastica at this aneurysm predilection site. RESULTS: Case 1: A 54-year-old woman with 2 dissecting aneurysms of the bilateral vertebral arteries (VA) who died from recurrent subarachnoid hemorrhage (SAH). Case 2: A 53-year-old woman who died from SAH. Microscopically, all 3 vertebral aneurysms were typical transmural dissecting aneurysms. They manifested areas of focal, severe degeneration of the elastic lamina and calcification at VA sites proximal to the aneurysms. These lesions could be differentiated from secondary changes attributable to the aneurysms because of their separate location only proximal to the site of aneurysmal rupture. Atherosclerotic changes were minimal in both cases. In the controls, the degenerative state of the elastic lamina of the VA reflected an atherosclerotic process. CONCLUSIONS: We postulate that focal degeneration of elastic tissue not involved in the atherosclerotic process was the vasculopathy resulting in aneurysm formation in our SAH cases.

Aortic Dissection↗
PubMed2002

Attenuated nuclear shrinkage in neurons with nuclear aggregates--a morphometric study on pontine neurons of Machado-Joseph disease brains.

Nuclear aggregates (NAs) and neurodegeneration in brains from patients with Machado-Joseph disease (MJD) are both triggered by pathological expansion of CAG/polyglutamine repeat in ataxin-3, but it remains to be clarified whether NA formation is associated with accelerated neurodegeneration. In an attempt to clarify a possible influence of NAs on neurons in human brains, we quantified the size and deformity of neuronal nuclei (those with or without NAs, separately) cross-sectioned on pontine preparations of autopsied brains from four patients with MJD and five controls. Nuclear shrinkage and deformity were more marked in MJD brains than in controls, and these changes were attenuated in neurons harboring NAs. NAs of MJD are presumably linked to a mechanism that attenuates rather than accelerates nuclear shrinkage and deformity. This finding leads us to consider that NAs are not necessarily toxic to neurons in diseased human brains.

Adult↗
PubMedDate not supplied

Intrathecal mepivacaine and prilocaine are less neurotoxic than lidocaine in a rat intrathecal model.

BACKGROUND AND OBJECTIVES: Histologic evidence of the comparative neurotoxicity of lidocaine, mepivacaine, and prilocaine is incomplete. We compared the intrathecal neurotoxicity in rats among these 3 drugs based on morphologic and neurofunctional findings. METHODS: Rats (n=169) randomly received 0.12 microL/g of 0%, 2%, 5%, 7.5%, 10%, or 20% lidocaine, mepivacaine, or prilocaine or 25% glucose dissolved in distilled water via a chronically implanted intrathecal catheter. The effect of the agents on neurofunction was evaluated by movement of the hind limb (behavior test) and by sensory threshold (paw-stimulation test). The L1 spinal cord, the posterior and anterior roots, and the cauda equina were removed en bloc 5 days later and examined by light and electron microscopy. RESULTS: A significant decrease in sensory threshold or irreversible hind-limb limitation was observed only in rats receiving 20% lidocaine. Morphologic abnormalities characterized by axonal degeneration were observed in rats receiving > or =7.5% lidocaine, 20% mepivacaine, and 20% prilocaine, at the posterior white matter and the proximal portion of the posterior root just at the entrance into the spinal cord. The incidence of lesions was significantly higher in rats receiving lidocaine than mepivacaine and prilocaine. CONCLUSION: It is suggested that intrathecal mepivacaine and prilocaine are less neurotoxic than highly concentrated lidocaine in a rat intrathecal model.

Anesthetics, Local↗
PubMedDate not supplied

Neurotoxicity of intrathecally administered bupivacaine involves the posterior roots/posterior white matter and is milder than lidocaine in rats.

BACKGROUND AND OBJECTIVES: Clinical and laboratory studies suggest that lidocaine is more neurotoxic than bupivacaine. However, histological evidence of their comparative neurotoxicity is sparse. We thus pathologically and functionally compared the intrathecal neurotoxicity of these agents. METHODS: Rats received 0.12 microL/g body weight lidocaine (0%, 2%, 10%, or 20%) or bupivacaine (0%, 0.5%, 2.5%, or 5%) in distilled water via an intrathecal catheter. The influence of high osmolarity was also examined using 5% bupivacaine in 20% glucose solution (5% BG) and a control 25% glucose solution. The L3 spinal cord, the posterior and anterior roots, and the cauda equina were examined by light and electron microscopy. Walking behavior and sensory threshold were investigated as neurofunctional tests. RESULTS: The posterior root and posterior white matter showed axonal degeneration in rats treated with 10% and 20% lidocaine and 5% bupivacaine in distilled water (5% BDW) and in 5% BG, but not in rats treated with 2% lidocaine, 0.5% and 2.5% bupivacaine, distilled water, or 25% glucose solution. The histological damages were more severe in 20% lidocaine-treated rats than in 5% bupivacaine-treated rats. The damage of posterior white matter was observed only when the posterior root was severely injured. No significant difference of histological findings was observed between 5% BDW and 5% BG. Functional abnormalities were found only in rats treated with 20% lidocaine. CONCLUSIONS: The neurotoxic lesions caused by bupivacaine and lidocaine were indistinguishable in the primary site and the extending pattern, such as axonal degeneration originating from the posterior roots and extending to the posterior white matter. The intrathecal neurotoxicity is greater in lidocaine than in bupivacaine.

Anesthesia Recovery Period↗
PubMedDate not supplied

Intrathecal lidocaine causes posterior root axonal degeneration near entry into the spinal cord in rats.

BACKGROUND AND OBJECTIVES: The neurotoxicity of lidocaine is not fully understood, and the primary lesion of lidocaine-induced spinal neurotoxicity has not been defined. Here we examine the effects of various concentrations of intrathecally administered lidocaine. METHODS: Forty-seven Wistar rats received 20%, 10%, 7.5%, 5%, 3%, or 0% lidocaine dissolved in distilled water, or 25% glucose solution via a chronically implanted intrathecal catheter. The spinal cord at L1, posterior and anterior roots, and cauda equina were dissected out 5 days later, sectioned, and prepared for light and electron microscopy. The effect of the agent on function was evaluated by movement of the hind limb (behavior test) and by sensory threshold (paw stimulation test). Another 7 rats were used to establish the precise locus of lesion within the posterior root after intrathecal 20% lidocaine injection. RESULTS: Rats treated with 10% or 20% lidocaine developed lesions both in the posterior roots and posterior columns, characterized by axonal degeneration. Rats injected with 7.5% lidocaine developed degenerative lesions limited to the posterior roots. Lesions in the posterior roots were localized to the proximal portion of the roots. Injections of 5% or less lidocaine did not cause any pathological changes. One of 5 rats receiving 20% lidocaine showed hind-limb paralysis for 4 days, but the remaining 4 rats recovered within 4 days after drug injection. Rats injected with < or = 10% lidocaine were completely recovered within 4 hours. The threshold for paw stimulation was significantly decreased in rats injected with 20% lidocaine. CONCLUSION: Our results suggest that spinal lidocaine neurotoxicity after supra-clinical concentrations of lidocaine is limited initially to the posterior roots at their entry to the spinal cord, and the extent and severity of the lesions are closely associated with lidocaine concentration. Unlike severe lesions in rats injected with 20% lidocaine, mild lesions caused by lower concentrations may not manifest neurofunctional deficits.

Anesthetics, Local↗