Biomedical subjects

Shigeo Murayama

Publications and source records attributed to Shigeo Murayama.

13 recordsLinked to original sources

PubMed2003

Impaired motor coordination in mice lacking neural recognition molecule NB-3 of the contactin/F3 subgroup.

The neural recognition molecule NB-3, which belongs to the contactin subgroup of the immunoglobulin superfamily, is expressed exclusively in the nervous system and mainly upregulated at the early postnatal stage during mouse brain development. The expression of NB-3 in the cerebellum increases until adulthood. In contrast, the expression in the cerebrum declines to a low level after postnatal day 7. To characterize the functional roles of NB-3 in vivo, we generated NB-3-deficient mice by substituting a part of the NB-3 gene with the beta-galactosidase (Lac Z) gene. Complete overlap of the Lac Z expression in the heterozygous mouse brain with the NB-3 immunostaining pattern in the rat cerebellum and with the previously reported pattern of in situ hybridization of NB-3 transcripts indicated that Lac Z expression reflects the expression of NB-3 in the mouse brain. NB-3-deficient mice were viable and fertile. The formation and organization of all nuclei and layers throughout the brains of mutant mice appeared normal. Behavioral tests to examine motor function showed that the mice deficient for NB-3 were slow to learn to stay on the rotating rod in the rotorod test during repeated trials, and that they displayed dysfunction of equilibrium and vestibular senses in the wire hang and horizontal rod-walking tests. In contrast, the mutant mice showed no difference of grasp force from the wild-type mice. Thus, NB-3-deficient mice are impaired in motor coordination.

Animals↗

PubMed2003

Acute human T-lymphotropic virus type 1-associated myelopathy: a clinicopathologic study.

BACKGROUND: Recently, acute human T-lymphotropic virus type 1-associated myelopathy (HAM) was reported clinically without pathologic information. We report an autopsy case of acute HAM. OBJECTIVE: To report the case of a 52-year-old man with acute-onset gait disturbance followed by rapidly progressive paraplegia, who died 9 months later. RESULTS: The postmortem study showed swelling of the thoracic spinal cord. Histologically, there was inflammation and vacuolation in the white matter. CONCLUSION: We propose that these pathologic findings, mimicking tropical spastic paraparesis, may represent the characteristic pathologic features of acute HAM.

Autopsy↗

PubMed2003

Accumulation of phosphorylated alpha-synuclein in aging human brain.

Alpha-synuclein in Lewy bodies (LBs) is phosphorylated at Ser129. We raised monoclonal and polyclonal antibodies to this phosphorylation site (psyn) and examined 157 serial autopsy brains from a geriatric hospital. Anti-psyn immunoreactivity was observed in 40 of these cases (25.5%). Immunohistochemistry revealed 4 novel types of pathology: diffuse neuronal cytoplasmic staining (pre-LB); neuropil thread-like structures (Lewy threads); dot-like structures similar to argyrophilic grains (Lewy dots); and axons in the white matter (Lewy axons). This novel pathology was abundantly present around LBs and also involved the limbic subcortical white matter, the cerebral cortical molecular layer, and the spongiform changes of the medial temporal lobe associated with cases of dementia with LBs (DLB). The phosphorylated alpha-synuclein was limited to the temporal lobe in cases of Parkinson disease, spread from the temporal lobe to the frontal lobe in cases of DLB transitional form and further spread to the parietal and occipital lobes in DLB neocortical form. Our findings suggest that LB-related pathology initially involves the neuronal perikarya, dendrites, and axons, causes impairment of axonal transport and synaptic transmission, and later leads to the formation of LBs, a hallmark of functional disturbance long before neuronal cell death.

Aged↗

PubMed2003

[Marked decrease of intracranial atherosclerosis in contrast with unchanged coronary artery stenosis in Japan].

We conducted comparative studies on intracranial atherosclerosis and coronary artery stenosis over the past 28 years. Two-year consecutive autopsy case studies from an urban geriatric hospital between 1974-1975 (Group I. 484 cases). 1986-1987 (Group II, 504 cases) and 2000-2001 (Group III, 273 cases) were employed. Atherosclerotic changes of the bilateral middle cerebral arteries and basilar artery were semiquantitatively evaluated as none (0), mild (1), moderate (2) and severe (3) and values of the 3 arteries were totalled to give a value of 0-9 which was taken as the intracranial atherosclerotic index (ICAI). The coronary stenotic index was calculated as previously reported (Sugiura et al 1969). ICAI and CSI were directly compared with each other, together with risk factors for each, including mean blood pressure (BP), serum level of total cholesterol (Tch) and the history of diabetes mellitus (DM+). Chronologically ICAI decreased dramatically but CSI did not change at all. There was continuous lowering of BP, elevation of Tch and increased incidence of DM+. There was a significant positive correlation in BP in relation to both ICAI and CSI (p < 0.01). DM+ vs. CSI (p < 0.01) and ICAI (p < 0.05), and Tch vs. CSI (p < 0.01) but not ICAI. Regression analysis highlighted age and BP as major risk factors for ICAI. Our study provides the first morphological confirmation of marked decrease of the intracranial atherosclerosis in the recent 28 years, in contrast with unchanged coronary stenosis in Japanese elderly subjects.

Aged↗

PubMed2002

Isoaspartate formation at position 23 of amyloid beta peptide enhanced fibril formation and deposited onto senile plaques and vascular amyloids in Alzheimer's disease.

Senile plaques and amyloid-bearing vessels consisting of fibrillar amyloid beta peptides (A beta) are characteristic neuropathological features of Alzheimer's disease (AD). A beta undergo spontaneous post-translational modifications, such as isomerization and racemization, at their aspartyl residues in AD brains. Here we present evidence that A beta isomerized at position 23 are deposited on plaques and vascular amyloids using an anti-isomerized A beta antibody. In vitro experiments showed that isomerization at position 23, but not position 7, enhanced aggregation. Furthermore, A beta with the Dutch mutation, but not the Flemish mutation, also showed greatly enhanced aggregation. These results suggest that mutations or modifications at positions Glu 22 and Asp 23 have a pathogenic role in the deposition of A beta. The development and progression of sporadic AD may be accelerated by spontaneous isomerization at position 23 of A beta.

Aged↗

PubMed2002

Severe involvement of the ambient gyrus in a case of dementia with argyrophilic grain disease.

We report here the severe involvement of the ambient gyrus in a case of argyrophilic grain (AG) dementia (AGD). The patient was a 78-year-old man who was first presented with prosopagnosia (agnosia of the face) at age 68, which was followed by progressive mental decline and the patient's death in a state of tetraplegia. The postmortem study showed severe atrophy of the medial temporal lobe with anterior gradient, most prominent in the ambient gyrus. Histologically, numerous AGs, pretangles and coiled bodies were detected by Gallyas-Braak (G-B) silver staining and also by immunostaining with various anti-tau antibodies in the affected area. Tau-immunoreactive ballooned neurons were also present. Neuronal loss and gliosis with laminar sponginess were evident in the ambient gyrus. Diffuse plaques were seen in the neocortex and frequently associated with clusters of AGs, which were morphologically distinct from neuritic plaques. Neurofibrillary tangles were localized in the entorhinal area. Vascular lesions were very scanty. Thus, this case fulfilled the morphological criteria of AGD. It is still unclear whether AG itself causes neuronal degeneration leading to dementia. The present case may reflect the importance of the ambient gyrus in the center of neuronal degeneration in AGD.

Aged↗

PubMed2002

Ubiquitin-positive neuronal and tau 2-positive glial inclusions in frontotemporal dementia of motor neuron type.

Attempts at classification of fronto-temporal dementias have not yet been completely successful. We report ten cases of sporadic fronto-temporal dementia (FTD) with ubiquitin-positive neuronal inclusions in cortex or in motor neurons in brain stem or spinal cord, which may contribute to the classification of FTD. Marked variation in clinical presentation as well as in pathological findings was the rule in all cases. Dementia was a prominent feature. Only one case had clinical features suggestive of motor neuron disease. Three of four younger onset cases displayed an especially severe atrophy of the temporal lobes, the basal ganglia and the substantia nigra. This contrasted with the other seven cases in which the fronto-temporal atrophy and changes in basal ganglia and substantia nigra were variable and sometimes mild. In addition to the presence of ubiquitin-reactive, but tau-and silver impregnation-negative neuronal inclusions, all cases demonstrated tau 2-positive glial inclusions, similar to those recently reported in three motor neuron disease cases with dementia. The glial inclusions were not visible with antibody to tau 1. Reaction with antibody to alpha-synuclein was invariably negative. If the combination of ubiquitin-positive neuronal and tau 2-positive glial inclusions is found to be consistently present in FTD of motor neuron type, this feature will provide a firmer basis for this diagnosis than previously available.

Adult↗

PubMed2002

Niemann-Pick type C disease: accelerated neurofibrillary tangle formation and amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity.

Niemann-Pick type C disease is a neurovisceral storage disorder. Neurofibrillary tangles similar to those in Alzheimer's disease have been reported in most juvenile/adult patients without amyloid beta protein (Abeta) deposits. Recently, we found deposits of Abeta in the form of diffuse plaques in three (31- and 32-year-old sisters and a 37-year-old man) of nine Niemann-Pick type C disease patients, who presented with most severe tauopathy and with numerous neurofibrillary tangles. Abeta deposits were not detected in any of the control brains of patients younger than age 42 years. These three patients with Abeta deposit all were homozygotes of apolipoprotein E epsilon 4. Our study suggested that NPC1 gene mutations combined with homozygosity of apolipoprotein E epsilon 4 alleles could manifest neuropathology similar to that of Alzheimer's disease. Investigation of these patients may provide an important clue for understanding the pathogenesis of Alzheimer's disease.

Adult↗

PubMed2002

Utilization behavior as a white matter disconnection syndrome.

We report a case of utilization behavior that was examined neuropathologically. A 72-year-old right-handed male patient, who was admitted with a complaint of transient loss of consciousness, displayed utilization behavior several times. He used daily objects that were placed in front of him, such as a teacup and a toothbrush, without instructions to do so. If the examiner asked the patient not to use the objects, the patient did not use them. MRI revealed acute infarction of the left superior frontal gyrus, where decreased blood flow was revealed by SPECT. The patient died of an acute worsening of dilated cardiomyopathy. Neuropathological examination demonstrated an acute phase infarction of the subcortical white matter of the left superior frontal lobe, which correlated well with neuroradiological findings. Utilization behavior has been thought a "frontal lobe symptom". However, we propose that utilization behavior might be considered a white matter disconnection syndrome.

Aged↗

PubMed2002

Severe involvement of ambient gyrus in dementia with grains.

Argyrophilic grains are detected as punctate or filiform structures in the neuropil of the medial temporal lobe, and dementia with grains (DG) is defined as a form of dementia with argyrophilic grains as the only explainable cause. We found argyrophilic grains in 43.2% of our 190 serial autopsy brains (mean age, 79.7 yr) from a community-based geriatric hospital, but only 20% of these argyrophilic grain-positive brains fulfilled the criteria for DG. To determine if there are structural differences between cognitively normal cases with argyrophilic grains (CNG) and DG, we studied 14 brains with CNG and 15 brains with DG. All cases of DG had severe atrophy of the ambient gyrus (the junction between temporal lobe and amygdala) with spongiosis, neuronal loss, and gliosis, as well as many grains, pretangles, coiled bodies, and tau-immunoreactive astrocytes. Comparable changes were not present in the ambient gyrus of CNG brains. The temporal neocortex and hippocampus were relatively spared in DG, in contrast to Alzheimer disease. Our study suggests that selective severe involvement of the ambient gyrus may explain the clinical manifestations of a limbic-type dementia in DG.

Aged↗

PubMed2002

[Overlap syndrome of systemic lupus erythematosus and dermatomyositis presented a large demyelinating subcortical lesion mimicking brain tumor and high level of CSF antineuronal and serum anti-ribosomal P antibodies].

We reported a 50-year-old man with an overlap syndrome of dermatomyositis and SLE, whose magnetic resonance image of the brain showed a rapidly increasing large tumor-like focal lesion unequally enhanced by Gd-DTPA in the left frontal lobe. Its pathological finding by the brain biopsy was fibrinoid necrosis, inflammatory cell aggregation around blood vessels and many myelin-laden macrophages with central necrosis. Although many cases of blood vessel injury are reported in CNS lupus, in this case the brain lesion partly took reversible course and neural symptoms such as paresis were slight and the lesion well responded to steroid. Moreover we considered that the measurement of serum anti-ribosomal P and CSF antineuronal antibodies are useful to diagnose cases as CNS lupus.

Autoantibodies↗

PubMed2002

[Multiple system atrophy with a-/hypo-ceruloplasminemia: distribution of iron in brains of 2 autopsy cases].

OBJECTIVE: We presented first two cases of multiple system atrophy (MSA) with a-/hypo-ceruloplasminemia (hypo-Cp). To know whether hypo-Cp was a cause of MSA, we investigated distribution of iron in brains. METHODS: Investigating history, neurological sings and symptoms, neuroimagings, and neuropathological findings of the 2 cases, we demonstrate that these 2 cases were typical MSA. Serum ceruloplasmin (Cp) values of two cases were investigated, as well as those of 14 MSA patients diagnosed after the 2 cases. In the 2 cases, we compared distribution of lesions and distribution of iron depositions revealed by Berlin blue stain (iron stain). Further, we compared depositions of iron in substantia nigra, putamen, and dentate nucleus of the 2 cases with those of 4 control MSA, 2 Parkinson's disease (PD), 2 amyotrophic lateral sclerosis (ALS), and 3 controls. RESULTS: Case 1 was 68-year-old man who developed gait disturbance, and had anti-Parkinson disease drugs after diagnosis of PD. Parkinsonism was progressed, and became bed-ridden after 6 years when he died. Neuropathological finding was typical MSA from distribution of lesions, as well as existence of GCIs and NCIs. Case 2 was 61-year-old man who developed parkinsonism. After 9 years, he had tracheostomy, and after 11 years died of renal failure. Neuropathological finding was typical MSA. With an investigation of serum Cp values of clinically diagnosed 14 MSA patients, we found 2 other cases of MSA with hypo-Cp. Iron stain of the 2 brains revealed that iron depositions were found in substantia nigra and putamen, but were not found neither in pontine base, cerebellum, nor inferior olive. Iron depositions were also seen in substantia nigra and putamen of control MSA cases as same degree as MSA with hypo-Cp, but iron depositions were fewer in PD, ALS and controls. CONCLUSION: Clinico-pathological findings of the the 2 cases were those of typical MSA, but were not same as those of previously reported hypo-Cp. Previous reports suggested iron depositions as a cause of brain lesions, but, we concluded that, in the 2 cases, iron depositions were not a direct cause of MSA lesions. However, high incidence of association of hypo-Cp and MSA shown in our study suggests a relation between hypo-Cp and MSA.

Aged↗

PubMedDate not supplied

Magnetic resonance imaging findings of Machado-Joseph disease: histopathologic correlation.

PURPOSE: To determine the characteristic magnetic resonance imaging (MRI) findings of early- and late-stage Machado-Joseph disease (MJD) and to examine correlation with pathologic specimens. PATIENTS AND METHODS: Four patients genetically diagnosed with MJD and a familial case of MJD were all examined using MRI. Machado-Joseph disease was pathologically confirmed in one of the four genetically diagnosed patients, and the findings were compared with the MRI results. RESULTS: In all three patients who had MJD for less than 8 years, MRI confirmed mild cerebellar atrophy, particularly in the vermis, and atrophic changes in the superior cerebellar peduncle. Mild pontine atrophy was observed in these three patients. Atrophic changes in the pontine tegmentum were more prominent than those of the pontine base in these patients. Two of the three patients showed mild frontal atrophy. Of the five total patients, two had the disease for over 10 years and showed progressive atrophy of the brainstem and mild frontal atrophy. These two patients also showed pallidal atrophy. One autopsied case in which the disease duration was 17 years showed a typical pathologic picture of MJD. Macroscopic findings for this patient showed marked atrophy of the pons, mild cerebellar atrophy (particularly in the vermis), marked atrophy of the superior cerebellar peduncle, severe involvement of motor nuclei, and atrophy and discoloration of the pallidum and subthalamic nuclei. CONCLUSION: In the early stages of MJD, mild pontine atrophy, particularly in the tegmentum, and mild cerebellar atrophy are typical MRI findings. Atrophic changes in the brainstem may be progressive. Pallidal atrophy may be observed in patients with long disease duration. These findings correlated with the pathologic findings.

Adult↗