記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2020.117068

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We examined the diagnostic value of brain perfusion single-photon emission computed tomography (SPECT) using voxel-based statistical analysis with CT-based attenuation correction (CT-AC) by comparing it to that with Chang's AC in mild cognitive impairment (MCI) patients and attempted to locate brain areas that are good indicators predicting the progression of MCI. METHODS: Twenty-six individuals matched for age, educational background and initial Mini-Mental State Examination (MMSE) score of more than 24 underwent SPECT with N-isopropyl-4-[123I]iodoamphetamine and were assigned to 2 groups: the stable MCI (S-MCI) group comprising 11 subjects who maintained their MMSE score (mean 27.0) during at least a 1-year follow-up period (mean 37.2 months) and the progressive MCI (P-MCI) group comprising 15 subjects whose MMSE scores decreased by 3 or more points (from 26.4 to 21.4, mean). The diagnostic values of the two AC methods for discriminating P-MCI from S-MCI were compared using voxel-based statistical analysis in the lobe (Level 2) and lobule/gyrus levels (Level 3). RESULTS: Receiver operating characteristic analysis revealed that the area under the curve (AUC) was higher with CT-AC than with Chang's AC in the left temporal and limbic lobes in Level 2. In Level 3, the AUC in the left middle temporal gyrus was higher with CT-AC (0.852) than with Chang's AC (0.827). There were differences between the gyri/lobules that showed higher AUCs with CT-AC and those that showed higher AUCs with Chang's AC. When the gyri with the 4 highest AUCs were combined, AUC (0.897) and accuracy (84.6%) were better with CT-AC than with Chang's AC (0.806 and 80.8%). Surprisingly, the AUCs in the posterior cingulate gyrus and precuneus, excluding the AUC in the right precuneus with Chang's AC (0.715), were no more than 0.70 and less useful. CONCLUSIONS: CT-AC may allow brain perfusion SPECT to reflect more exact neuropathic changes in MCI that would cause progression of early AD. CT-AC in conjunction with voxel-based statistical analysis could possess higher diagnostic accuracy for exacerbation of disease implying early Alzheimer changes in MCI patients, with decreases in cerebral perfusion in the left temporal and limbic lobes representing good indicators.

DOI： 10.1007/s12149-020-01477-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Guillain-Barré syndrome (GBS) comprises a group of polyneuropathies characterized by rapid progression of limb paralysis. Various subtypes of GBS have been reported. The oculopharyngeal subtype of GBS is currently understood to be primarily a cranial polyneuropathy without limb weakness or cerebellar ataxia. In our case of 62-year-old man, gastrointestinal infection was followed by paranesthesia of the hands. He had bilateral ptosis, pharyngeal disorder, and tongue and bifacial weakness. We diagnosed oculopharyngeal subtype of GBS. It responded to intravenous immunoglobulin. This case highlights the need for further characterization of unusual GBS subtypes.

DOI： 10.2169/internalmedicine.3395-19

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

© 2020 Societas Neurologica Japonica. All rights reserved. Epilepsy surgery for patients with drug-resistant epilepsy after anti-N-methyl-D-aspartate (NMDA) receptor encephalitis has been rarely reported. The present study reports two patients with anti-NMDA receptor encephalitis, who later underwent epilepsy surgery due to drug-resistant epilepsy. The patients had refractory status epilepticus in the acute phase. The cerebrospinal fluid was positive for anti-NMDA receptor antibodies. Systemic corticosteroid therapy and plasma exchange were effective. Seizure control, however, worsened over several months after discharge, and was refractory to antiepileptic drugs. They underwent palliative epilepsy surgery, and their seizure control improved. Epilepsy surgery should be considered in patients with drug-resistant epilepsy after anti-NMDA receptor encephalitis.

DOI： 10.5692/clinicalneurol.cn-001266

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.104456

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ensci.2019.100210

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ensci.2018.12.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background In a previous phase 3 study in patients with amyotrophic lateral sclerosis (ALS), edaravone did not show a significant difference in the Revised ALS Functional Rating Scale (ALSFRS-R) score compared with placebo. Post-hoc analysis of these data revealed that patients in an early stage with definite or probable diagnosis of ALS, defined by the revised El Escorial criteria, who met a select set of inclusion criteria showed a greater magnitude of effect than did the full study population. We aimed to substantiate this post-hoc result and assess safety and efficacy of edaravone in a phase 3 trial that focused on patients with early stage ALS who met the post-hoc analysis inclusion criteria.
Methods In this phase 3, randomised, double-blind, parallel-group study, patients aged 20-75 years with ALS of grade 1 or 2 in the Japan ALS Severity Classification, scores of at least 2 points on all 12 items of ALSFRS-R, forced vital capacity of 80% or more, definite or probable ALS according to the revised El Escorial criteria, and disease duration of 2 years or less were recruited from 31 hospitals in Japan. Eligible patients also had a decrease of 1-4 points in the ALSFRS-R score during a 12-week observation period before randomisation. Patients meeting all criteria were then randomly assigned 1:1 to receive 60 mg intravenous edaravone or intravenous saline placebo for 6 cycles (4 weeks per cycle with 2 weeks on, 2 weeks off) for a total treatment duration of 24 weeks. In cycle 1, the study drug or placebo was administered once per day for 14 days within a 14 day period, followed by the drug-free period. In cycle 2 and thereafter, the study drug or placebo was administered for 10 days within a 14 day period, followed by a 2 week drug-free period. Participants and investigators, including those assessing outcomes, were masked to treatment allocation. The primary efficacy outcome was the change in ALSFRS-R score from the baseline to 24 weeks (or at discontinuation if this was after the third cycle) after randomisation. The primary outcome was assessed in all patients who had received at least one treatment infusion, had at least one assessment post-baseline, and reached the end of cycle 3. For patients with missing values at the end of cycle 6, data were imputed by the last observation carried forward (LOCF) method, provided the patients had completed at least cycle 3. Safety was assessed in all patients who had received at least one treatment infusion and had at least one assessment post-baseline. This trial is registered with ClinicalTrials.gov, NCT01492686.
Findings Between Nov 28, 2011, and Sept 3, 2014, we screened 213 patients, and enrolled 192 as potential participants. Of these, 137 patients completed the observation period: 69 were randomly assigned to receive edaravone, and 68 were randomly assigned to receive placebo. 68 patients taking edaravone and 66 taking placebo were included in the primary efficacy analysis. For the primary outcome, the change in ALSFRS-R score was -5.01 (SE 0.64) in the edavarone group and -7.50 (0.66) in the placebo group. The least-squares mean difference between groups was 2.49 (SE 0.76, 95% CI 0.99-3.98; p = 0.0013) in favour of edaravone. Treatment-emergent adverse events were reported in 58 (84%) patients receiving edaravone and 57 (84%) patients receiving placebo. 11 (16%) patients taking edaravone and 16 (24%) taking placebo had serious adverse events, and one (1%) patient receiving edaravone and four (6%) patients receiving placebo had adverse events (one dysphagia in edaravone group and one dyspnoea, two respiratory disorder, and one rash in the placebo group) that led to withdrawal.
Interpretation Edaravone showed efficacy in a small subset of people with ALS who met criteria identified in post-hoc analysis of a previous phase 3 study, showing a significantly smaller decline of ALSFRS-R score compared with placebo. There is no indication that edaravone might be effective in a wider population of patients with ALS who do not meet the criteria.

DOI： 10.1016/S1474-4422(17)30115-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 66-year-old man presented with headache and ophthalmalgia. Diplopia developed, and he was hospitalized. The left eye had abducent paralysis and proptosis. We diagnosed him with Tolosa-Hunt syndrome and administered methylprednisolone at 1 g/day for 3 days. However, the patient did not respond to treatment. No abnormality was found on his MRI or cerebrospinal fluid examination. Tests showed his serum immunoglobulin G4 and antineutrophil cytoplasmic antibody titers were within normal limits. He also had untreated diabetes mellitus (HbA1c 9.2). One week after first presenting with symptoms, herpes zoster appeared on the patient's dorsum nasi, followed by keratitis and a corneal ulcer. Herpes zoster ophthalmicus with ophthalmoplegia was diagnosed. We began treatment with acyclovir (15 mg/kg) and prednisolone (1 mg/kg, decreased gradually). Ophthalmalgia and the eruption improved immediately. The eye movement disorder improved gradually over several months. It is rare that diplopia appears prior to cingulate eruption of herpes zoster ophthalmicus. We speculated that onset of the eruption was inhibited by strong steroid therapy and untreated diabetes mellitus.

DOI： 10.5692/clinicalneurol.cn-000972

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores >2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-12], forced vital capacity >80%, definite or probable ALS, and disease duration <2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was 4.1 +/- 3.4 and 6.9 +/- 5.1 in the E-E group and P-E group, respectively, while it was 8.0 +/- 5.6 in the E-E group and 10.9 perpendicular to 16.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.

DOI： 10.1080/21678421.2017.1364269

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Following the first phase III study of edaravone for amyotrophic lateral sclerosis (ALS), this extension study was performed to evaluate longer -term efficacy and safety. Patients given edaravone in the first 24 -week phase III study (Cycles 1-6) were randomised to edaravone (E -E) or placebo (E -P) in the subsequent 24 -week double-blind period (Cycles 7-12). Patients given placebo in phase III were switched to edaravone (P -E). Subsequently, all patients received edaravone for 12 weeks (Cycles 13-15). Efficacy endpoints included revised ALS Functional Rating Scale (ALSFRS-R) score. Analysis populations were the full analysis set (FAS) and the efficacy -expected subpopulation (EESP) defined by post -hoc analysis of the first phase III study. The least -squares mean and standard error of the intergroup difference (E -E vs. E -P) of change in the ALSFRS-R score from Cycles 7-12 was 1.16 perpendicular to 1 0.93 (p= 0.2176) in the FAS, and 1.85 1.14 (p = 0.1127) in the EESP. The ALSFRS-R score changed almost linearly in the E -E group throughout Cycles 1-15 (60 weeks). The incidence of serious adverse events associated with ALS progression was higher in E -E than in E -P. Edaravone might have potential efficacy for up to 15 cycles when used to treat patients in the EESP with careful safety monitoring.

DOI： 10.1080/21078421.2017.1362000

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities. An electroencephalograph showed generalized periodic discharge and a triphasic wave pattern. We thought that the cause of disturbance in consciousness was Cefepime-induced encephalopathy, and stopped administration of Cefepime. A few days later, he became clear, and the myoclonus and flapping disappeared. It was difficult to distinguish between non-convulsive status epilepticus and Cefepime-induced encephalopathy. However, since stopping Cefepime treatment had made the patient clear, we diagnosed his condition as Cefepime-induced encephalopathy, which often occurs in patients with renal or liver dysfunction, or in brain infarction or meningitis, which results in blood-brain barrier disruption. Thus, care should be taken when administering Cefepime to such patients.

DOI： 10.5692/clinicalneurol.cn-000898

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記述言語：英語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DUSTRI-VERLAG DR KARL FEISTLE  

Materials and methods: The present paper examines the brains and spinal cords in 7 patients with amyotrophic lateral sclerosis (ALS) receiving artificial respirator support in a totally locked-in state (TLS) neuropathologically in order to clarify whether any anatomical structures in the central nervous system are preserved. Results and conclusion: We found that the visual and olfactory pathways, hypothalamus, nucleus basalis of Meynert, and commissura anterior were remarkably well preserved, whereas the somatosensory, auditory, and gustatory pathways in the brain stem and/or spinal cord showed severe deterioration.

DOI： 10.5414/NP300859

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記述言語：英語  

The cornu ammonis 1 (CA1) area in the hippocampus of the parkinsonism-dementia complex (PDC) of Guam was examined quantitatively with special references to the number of neurons, intraneuronal (i) and extracellular (e) neurofibirillary tangles (NFTs), and TDP-43 (43-kDa trans-activation-responsive region DNA-binding protein)-immunopositive structures, in 24 Chamorro patients with PDC of Guam and seven control Chamorro Guamanians (both groups having no ischemic or anoxic complications). The results were that: (i) in the patients with mildly involved PDC, total numbers of neurons, iNFTs and eNFTs were almost the same as those of neurons of controls; (ii) in patients severely involved, total numbers of neurons, iNFTs and eNFTs decreased markedly; (iii) the decrease of the number of pyramidal neurons in CA1 with positive nuclear TDP-43 was intimately correlated with the decrease in total neuron numbers; (iv) whereas the numbers of neurons and TDP-43-immunopositive intracytoplasmic aggregation in the CA1 area were inversely correlated; and (v) depression of nuclear TDP-43 immuonostainability was not affected by the presence or absence of NFTs. In conclusion, hippocampal sclerosis exists in PDC; there is a possibility of elimination of eNFTs which appeared in the CA1 in patients with PDC and loss of the neurons correlates with disappearance of nuclear TDP-43, but not with appearance of intraneurocytoplasmic TDP-43 aggregation or iNFTs.

DOI： 10.1111/neup.12185

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記述言語：英語  

Diagnosing clinical progressive supranuclear palsy (PSP) is challenging. We hypothesize that there are more cases of pathological PSP than have been clinically identified, but its diagnosis is challenging because the initial lesions and progression of PSP have not yet been clarified. The purpose of our study was to clarify the incidence of PSP in consecutive autopsy cases and identify pathological characteristics of early PSP. We investigated 324 consecutive autopsy patients from a general geriatric hospital (age, mean±SD=82.5±8.7 years). Paraffin sections of the midbrain were immunostained with anti 4-repeat tau antibodies (RD4). We selected cases showing RD4-positive neurofibrillary tangles and tufted astrocytes in the midbrain sections. Then, we used anti-phosphorylated tau antibody to immunostain sections from the basal ganglia, subthalamic nucleus, midbrain, pons, medulla, and cerebellum. Of the 324 patients, 35 had RD4-positive structures in the midbrain. From these 35 cases, we excluded those for which autopsies confirmed definite PSP (n=5) and cases of corticobasal degeneration (n=1), Alzheimer's disease (n=11), dementia of grain (n=10), and neurofibrillary tangles predominant forms of senile dementia (n=2), leaving 8 cases. We diagnosed these 8 cases as pure PSP-type tauopathy. Pure PSP-type tauopathy was detected in 2.5% of the consecutive autopsy cases, and this incidence was 1.6 times greater than that of neuropathologically definite PSP. This pure PSP-type tauopathy likely indicates preclinical stages of PSP. Furthermore, the novel neuropathological finding, which we term "preclinical PSP," is unique and has not previously been reported. In order to elucidate the causes and pathological mechanisms of PSP, preclinical PSP should be investigated further.

DOI： 10.1272/jnms.82.266

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

BACKGROUND/AIMS: Donepezil is an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD). In this study, we used a voxel-based specific regional analysis system for AD (VSRAD) to analyze the hippocampal volume and to assess the pharmacologic effects of donepezil as a disease modifier. METHODS: A total of 185 AD patients underwent MRI, 120 (43 men and 77 women, 77.8 ± 7.1 years) without and 65 (29 men and 36 women, 78.4 ± 6.0 years) with donepezil treatment. VSRAD was compared in both groups and against a database of 80 normal subjects. The Z-score was used to assess the degree of hippocampal atrophy. RESULTS: No significant difference between the groups was found for age, sex, or Z-scores, but a significant difference was found for mean Mini-Mental State Examination (MMSE) scores (p = 0.02, Student's t test). Single regression analysis showed no significant association between Z-scores and MMSE scores in the treated group (p = 0.494), but a significant association in the untreated group (p = 0.001) was observed. This implies that the MMSE score becomes lower when the Z-score is higher in the untreated group, whereas there is no significant trend in the treated group. CONCLUSION: Donepezil affects the relationship between hippocampal volume and cognitive function and may therefore have a pharmacologic effect as a disease modifier.

DOI： 10.1159/000358510

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE AND METHODS: Dysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed. RESULTS AND CONCLUSIONS: Three mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations.

DOI： 10.1136/jnnp-2011-301339

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記述言語：英語  

We herein report the case of a 58-year-old man with advanced esophageal carcinoma who developed posterior reversible encephalopathy syndrome (PRES). He initially presented with a severe consciousness disturbance. A subsequent examination revealed hypercalcemia and an elevated serum parathyroid hormone-related peptide (PTHrP) level. Magnetic resonance imaging performed on admission and 24 days later showed reversible widespread white matter abnormalities, which confirmed a diagnosis of PRES. The patient's clinical and radiological manifestations improved upon normalization of the serum calcium level. To the best of our knowledge, this is the first report describing hypercalcemia-induced PRES occurring in association with elevated PTHrP.

DOI： 10.2169/internalmedicine.52.0444

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記述言語：日本語   出版者・発行元：The Medical Association of Nippon Medical School  

DOI： 10.1272/manms.9.33

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記述言語：日本語  

Seven autopsy patients with amyotrophic lateral sclerosis (ALS) in totally locked-in state (TLS) were examined neuropathologically. The patients were composed of 4 males and 3 females, and 3 with familial, 1 sporadic but with mutation in SOD1 gene, and 3 sporadic patients with unremarkable gene mutation. The brains weighed 715, 783, 1,019, 1,050, 1,170, 1,190 or 1,233 g. The tegmentum of the brain stem was markedly degenerated in every patient, and the tracts relating to the somatic sensory and auditory were involved in the lesions.

DOI： 10.5692/clinicalneurol.53.1399

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記述言語：英語  

In this study, we report the case of a 35-year-old woman with modified measles complicated by aseptic meningitis and subsequent optic neuritis. Although her initial manifestations were only flu-like symptoms without any Koplik's spots or skin rashes, virological testing confirmed an acute measles infection. Subsequently, right optic neuritis appeared after aseptic meningitis and was completely resolved following steroid pulse therapy. In general, modified measles is believed to be associated with mild symptoms and few neurological complications; however, our present observations demonstrated that modified measles can cause rapid neurological complications.

DOI： 10.7883/yoken.66.320

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記述言語：英語   出版者・発行元：SPRINGER HEIDELBERG  

DOI： 10.1007/s00415-011-6127-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Venous congestive myelopathy associated with spinal dural arteriovenous fistulas (DAVFs) is a treatable disorder that can be controlled without sequelae if it is diagnosed at an early stage. It is important to consider spinal DAVFs in the differential diagnosis based on clinical history and neurologic examination. We report the unique case of a patient with DAVFs at the craniocervical junction presenting with occipital/neck pain associated with sleep.

DOI： 10.2169/internalmedicine.51.6607

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background: Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by a combination of progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of DAP12 and TREM2, which constitute a receptor/adapter signaling complex expressed on osteoclasts, dendritic cells, macrophages, and microglia. No Japanese patients with TREM2 mutations have been reported previously.
Methods: We reported three siblings affected with NHD in a Japanese family. Amongst them, two died of NHD during the fourth decade of life. The analysis of genomic DNA, cDNA cloning, and western blot of lymphocyte proteins was performed on samples of the living patient. The transcriptome was studied in the autopsied brain of one patient.
Results: We identified a homozygous conversion of a single nucleotide T to C at the second position of intron 3 in the splice-donor consensus site (c.482+2T>C) of the TREM2 gene, resulting in exon 3 skipping and aberrant expression of truncated proteins. We identified 136 upregulated genes involved in inflammatory response and immune cell trafficking and 188 downregulated genes including a battery of GABA receptor subunits and synaptic proteins in the patient's brain.
Conclusions: This is the first report of a Japanese NHD family caused by a splicing mutation of TREM2 that induces both neuroinflammation and neurode-generation.

DOI： 10.1111/j.1468-1331.2010.03311.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

A 64-year-old female with a history of primary biliary cirrhosis and esophageal varices starting at age 39 was brought to our Stroke Care Unit by ambulance with right-side weakness and speech difficulty. Physical examination revealed right hemiparesis (including the face), sensory disturbances, pathological reflexes, and slightly decreased consciousness, with a Glasgow Coma Scale rating of E3V4M6. Flapping tremors and speech disturbance, as well as anarithmia, construction apraxia, and ideomotor apraxia, were noted, and her National Institutes of Health Stroke Scale score was 13. Initially, the patient was diagnosed with acute stroke and treated accordingly; however, subsequent findings from clinical images and electroencephalography led to a diagnosis of focal neurologic signs due to hepatic encephalopathy (HE). The patient had significantly reduced cerebral blood flow in the left side of the brain, probably due to microsurgical repair of an aneurysm done 2 years earlier. HE with exaggerated chronic liver damage might have made the previously silent ischemia clinically apparent. This interpretation is supported by the fact that the patient's neurologic deficits resolved once HE was adequately controlled. This case illustrates the need for careful assessment of background pathophysiology when diagnosing patients with stroke-like symptoms.

DOI： 10.1016/j.jstrokecerebrovasdis.2010.01.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We investigated whether a correlation exists between insulin resistance and the severity of cerebral white matter lesions among non-diabetic patients with ischemic stroke. METHODS: The subjects were 105 consecutive patients without diabetes who were hospitalized due to non-cardioembolic stroke. The insulin resistance was evaluated by a homeostasis model assessment of insulin resistance (HOMA-IR). The degrees of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) were evaluated by the brain MRI. The HOMA-IR values >or=2.5 were indicative of the insulin resistance. RESULTS: The presence of PVH and DSWMH were 86.7 and 83.8%, respectively. The ratio of insulin resistance increased with higher grades of PVH and DSWMH. The HOMA-IR level in grade 3 PVH was significantly higher than those in grades 0 and 1. The HOMA-IR level in grade 3 DSWMH was significantly higher than those in grades 0-2. Multiple linear regression analysis showed that HOMA-IR was significantly associated with PVH or DSWMH. CONCLUSION: It was found that insulin resistance correlated with white matter lesions among non-diabetic patients with non-cardiogenic ischemic stroke.

DOI： 10.1179/016164109X12608733393755

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

[(123)I]-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is useful for distinguishing multiple system atrophy (MSA) from Parkinson disease. In this study, longitudinal observation using MIBG myocardial scintigraphy was carried out in patients with MSA to evaluate the association of myocardial MIBG uptake with clinical features. A total of 96 MIBG examinations were performed in 52 patients with MSA. The heart/mediastinum (H/M) ratio of MIBG uptake at 240 minutes after injection was below the lower limit in 16 patients with MSA (31.3%). Overall, the H/M ratio correlated with neither disease duration nor severity. In the follow-up observations, the H/M ratio did not show any specific trends, in contrast with the continuous decrease observed in patients with Parkinson's disease. This data clearly showed that cardiac MIBG uptake cannot necessarily be preserved in patients with MSA and that approximately 30% of patients with MSA showed decreased MIBG uptake without any correlation to disease duration or severity.

DOI： 10.1002/mds.23338

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fabry disease is an X-linked lysosomal storage disease resulting from deficient activity of the enzyme alpha-galactosidase (alpha-Gal) A. It has been postulated that the accumulation of globotriaosylceramide in the endothelial cells of blood vessels may lead to thrombosis of the brain and other tissues. Recently, enzyme replacement therapy (ERT) for Fabry disease is available. A high incidence of thrombotic accidents in Fabry disease has been postulated. However, a systemic study on thrombosis in cases of Fabry disease has not been undertaken. To clarify the incidence of thrombosis in Fabry disease, we screened 65 patients with Fabry disease (49 hemizygotes and 16 heterozygotes) from 39 unrelated Japanese families. We found that ten patients with Fabry disease (7 hemizygous males and 3 heterozygous females) had experienced thrombotic accidents, under 45-years-old in 8 cases. These 10 patients showed the gene mutations of classical Fabry disease. Nine of these thrombotic patients developed brain infarctions, one man who had the complication of recurrent thrombophlebitis, and the remaining woman showed central retinal artery occlusion and thrombophlebitis. We demonstrated a high incidence of thrombosis in Fabry disease (15%). ERT should be performed in patients not only in hemizygous males but also in heterozygous females and started at their early ages.

DOI： 10.1016/j.jns.2009.02.319

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aims: Sporadic amyotrophic lateral sclerosis (ALS) is a progressive and invariably fatal disease involving the upper and lower motor neurones of adult humans. Among the neuropathological features of the disease, abnormalities in the protein-synthesizing system in motor neurones of the brainstem and spinal cord, such as a decrease of cytoplasmic RNA and rough endoplasmic reticulum (rER) (chromatolysis), defective editing of the Q/R site of the glutamate receptor subunit GluR2 mRNA, fragmentation of the Golgi apparatus and accumulation of ubiquitinated inclusions and abnormal TdP-43 protein have been reported to be essential for the degeneration. In relation to these features, although the possibility of ER stress has been reported in motor neurones of the brainstem and spinal cord of ALS patients, the rER itself has not been a main target of ultrastructural investigation. Methods: The present study examined the rER, ultrastructurally and quantitatively in the spinal anterior horn cells (AHCs) of 21 Japanese patients with sporadic ALS and eight Japanese control subjects. Results and conclusions: It was found that: (i) the rER cisternae in AHCs showing central chromatolysis were fragmented, but retained their width and had normally attached ribosomes, and (ii) the rER cisternae in shrunken AHCs were irregularly distended with detachment of the ribosomes, thus suggesting that (iii) ribosomal detachment was related to rER distention.

DOI： 10.1111/j.1365-2990.2008.00941.x

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記述言語：英語  

DOI： 10.1016/j.jocn.2007.10.006

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記述言語：英語  

DOI： 10.1002/mds.22031

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

TDP-43, a nuclear factor that functions in regulating transcription and alternative splicing, was recently identified as a component of the ubiquitin-positive, tau-negative inclusions specific for frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). In the present study, we carried out immunohistochemical and biochemical analyses of brains of Guamanians with the parkinsonism-dementia complex (G-PDC) using anti-TDP-43, anti-tau and anti-ubiquitin antibodies. Immunohistochemistry with anti-TDP-43 antibodies revealed various types of positive structures in the frontotemporal and hippocampal regions of G-PDC cases. Most of these structures were negative for tau. By immunoblot analysis with the TDP-43 antibody, an abnormal 45 kDa band, as well as a diffuse staining throughout the gel, was detected in the sarkosyl-insoluble fractions of G-PDC brains. Dephosphorylation has shown that abnormal phosphorylation takes place in the accumulated TDP-43 seen in FTLD-U and ALS. These results suggest that accumulation of TDP-43 is a common process in certain neurodegenerative disorders, including FTLD-U, ALS and G-PDC.

DOI： 10.1093/brain/awm065

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記述言語：日本語  

A 56-year old male presented with a sudden onset of bilateral hearing difficulty. He complained of dizziness and gait disturbance at the onset and subsequently developed bilateral hearing loss and tinnitus. Brain MRI revealed multiple infarcts in bilateral middle cerebellar peduncles, bilateral cerebellar hemispheres and the right cerebral peduncle. Three dimentional computed tomography angiography (3D-CTA) showed severe stenosis of bilateral vertebral arteries. Infarcts were located in the border zone between anterior inferior cerebellar artery (AICA) and superior cerebellar artery (SCA), suggesting hemodynamic infarctions. Auditory brain stem responses (ABR) were recorded three times. The initial ABR demonstrated all waves except for wave I on day 14. Wave I on the left was normal, while wave I peak latency on the right was prolonged. On day 61, all waves were recorded, although peak latencies of waves III to V and interpeak intervals of the wave I to III on the right side were prolonged. Involvements of the cochlear nerve and pontine auditory pathway were suggested from the ABR abnormalities in this case.

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1212/01.wnl.0000191329.34585.15

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

We established a histobiochemical approach targeting micron-order inclusion bodies possessing extensive aggregation properties in situ by using a nonchemical denaturant (oligomeric actin interacting protein 2/d-lactate dehydrogenase protein 2 [Aip2p/Dld2p]) with the combinatorial method of laser-microdissection and immunoblot analysis. As a model, pick bodies were chosen and laser-microdissected from three different brain regions of two patients with Pick's disease. Initially, 500 to 2000 pick bodies were applied onto SDS-PAGE gels after boiling in Laemmli's sample buffer according to established immunoblotting procedures; however, only faint signals were obtained. Following negative results with chemical denaturants or detergent, including 6 M guanidine hydrochloride, 8 M urea, and 2% SDS, the laser-microdissected pick bodies were pretreated with oligomeric Aip2p/Dld2p, which possesses robust protein unfolding activity under biological conditions. Strikingly, only one pick body was sufficient to illustrate an immunoblot signal, indicating that pretreatment with oligomeric Aip2p/Dld2p enhanced the immunoblot sensitivity by more than 100-fold. Pretreatment with oligomeric Aip2p/Dld2p also allowed us to quantify the total protein content of pick bodies. Thus, use of oligomeric Aip2p/Dld2p significantly contributed toward the acquisition of information pertaining to the molecular profile of proteins possessing an extensive aggregation property, particularly in small amounts.

DOI： 10.1016/j.ab.2005.09.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

To clarify the controversy concerning whether the cell death of motor neurons in ALS is apoptosis, we investigated the expression of Apaf-1 and caspase-9 mRNA in spinal cord tissue obained at autopsy from patients with ALS and controls using RT-PCR; the presence of in situ nuclear DNA fragmentation in motor neurons by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method; and immunocytochemical localization of Apaf-1 and caspase-3, which are known as promotors of apoptotic processes. Although Apaf-1 and caspase-9 mRNAs levels were increased in ALS, Apaf-1 immunoreactivity (IR) showed no significant difference between ALS and the control, and caspase-3 IR was not observed in ALS motoneurons, casting doubt on the notion that motor neurons in ALS undergo death by the classic apoptotic pathway. Although TUNEL-positive motor neurons were frequently observed in the anterior horn in ALS, these neurons always showed an atrophic cell body with a shrunken and pyknotic nucleus, indicating that they were at the terminal stage of degeneration. No apoptotic bodies were seen. These findings suggest that the mechanism of motor neuronal cell death in ALS might not be apoptosis, but some other as yet unidentified mechanism.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

We examined the autopsied brains of cases of 6 types of tauopathy: parkinsonism-dementia complex of Guam (PDC), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Pick disease, Alzheimer disease (AD), and myotonic dystrophy together with Guamanian controls. Light microscopy sections of these brains were examined using anti-tau antibodies. Tau-positive fine granules (TFGs) were globe-shaped, and 3 to 6 mum in diameter, were observed predominantly in the frontal white matter in 30 of the 35 patients with PDC. However, no TFGs were found in association with PSP, myotonic dystrophy, Pick disease, AD, or CBD. Western blot analysis of frozen brain tissue taken from the PDC cases revealed that the frontal cortex was hyperphosphorylated and contained 6 tau isoforms (3R+4R tau). However, in the present study, it was revealed that the novel TFGs in the white matter of patients with PDC was composed of 4R tau. Western blot analysis of sarkosyl-insoluble tau from the white matter of the PDC cases showed 2 major bands of 60 and 64 kDa and one minor band of 67 kDa. After dephosphorylation, these bands resolved into one major band of 4-repeat (4R) tau isoform and 3 minor bands of 3-repeat (3R) and 4R tau isoforms. Moreover, the TFGs observed in cases in which the number of neurofibrillary tangles (NFTs) was higher than the threshold level were not correlated with the presence of cortical NFTs. In conclusion, these novel TFGs were found almost exclusively in PDC brains and could therefore be considered as a characteristic neuropathologic marker of this particular tauopathy. The TFGs were hyperphosphorylated tau-positive structures that may be formed by a different mechanism from that used to produce cortical NFTs.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neurofibrillary tangles (NFTs) and neuropil threads (NTs), the major hallmark of Alzheimer disease (AD), are composed of the microtubule-associated protein tau that has undergone posttranslational modifications, including deamidation and isomerization on asparaginyl or aspartyl residues. Because such modifications represent protein aging, we generated 2 antibodies, TM4, specific for Asp-387 of tau, and iD387, specific for isoAsp-387 of tau, to investigate the evolution of NFTs and NTs. On Western blots of Sarkosyl-insoluble fractions, TM4 strongly labeled paired helical filament-tau (PHF-tau), whereas iD387 preferentially labeled PHF smear. Thus, it is reasonable to postulate that TM4-labeled tau (unmodified tau species) represents more recent deposition, and iD387-labeled tau (modified tau species) represents earlier deposition. Unexpectedly, TM4 immunostained even highly evolved NFTs, suggesting that deposition of newly produced tau continues until neuronal death. iD387 labeled the whole profile of NFTs up to distal dendritic branches, whereas TM4 staining was localized to particular portions of NFTs in proximal dendrites and neuronal perikarya. In NTs, TM4 preferentially labeled the outer portion, whereas iD387 intensely labeled the core portion. Based on TM4-positive NFT counts and total NFT counts, we speculate that NFTs in the human hippocampus are produced at a constant rate irrespective of the disease stage.

DOI： 10.1097/01.jnen.0000173890.79058.1d

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To clarify the controversy concerning whether the cell death of motor neurons in ALS is apoptosis, we investigated the expression of Apaf-1 and caspase-9 mRNA in spinal cord tissue obained at autopsy from patients with ALS and controls using RT-PCR; the presence of in situ nuclear DNA fragmentation in motor neurons by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method; and immunocytochemical localization of Apaf-1 and caspase-3, which are known as promotors of apoptotic processes. Although Apaf-1 and caspase-9 mRNAs levels were increased in ALS, Apaf-1 immunoreactivity (IR) showed no significant difference between ALS and the control, and caspase-3 IR was not observed in ALS motoneurons, casting doubt on the notion that motor neurons in ALS undergo death by the classic apoptotic pathway. Although TUNEL-positive motor neurons were frequently observed in the anterior horn in ALS, these neurons always showed an atrophic cell body with a shrunken and pyknotic nucleus, indicating that they were at the terminal stage of degeneration. No apoptotic bodies were seen. These findings suggest that the mechanism of motor neuronal cell death in ALS might not be apoptosis, but some other as yet unidentified mechanism.

DOI： 10.1111/j.1440-1789.2005.00648.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In case a pre-senile patient presented subacutely progressive dementia, secondary dementia, such as paraneoplastic neurological syndrome (PNS), hypothyroidism, confusion, early phase of primary degenerative dementia and prion diseases are to be considered. It is a case of pathologically confirmed, and clinico-pathologically assessed limbic encephalitis with cerebellar degeneration. The patient was a 63-year old male, with a well followed up medical history of gastric cancer 8 years earlier. Four weeks after he presented himself at our hospital his memory and disorientation progressively declined. A neurological examination revealed gaze nystagmus, with potential secondary dementia. However, no abnormal findings were detected from systemic radiological examination, or from chemical analyses. Two months later, after the onset of the disease, he presented additional symptoms, including seizure, gait disturbance, and insomnia. On admission, neurological examinations revealed gaze nystagmus and progression of dementia; however, his thought process was relatively preserved. No paroxysmal synchronized discharge was seen on electroencephalogram. Chest X-rays showed an inflammatory infiltration. In spite of anti-biotic medication, he died due to respiratory failure. The autopsy was limited to the brain. Histologically, limited lymphocytic infiltration into the hippocampus through the entorhinal cortex, with marked neuronal loss and gliosis was observed. Neuronophagia, microglial nodules, and perivascular lymphocytic infiltration were also seen. Additionally, most of the Purkinje cells in the cerebellum were lost, with Bergmann's gliosis and sparse lymphocytic infiltration. No tumor was observed in the brain. Pathological findings of the brain were compatible with paraneoplastic limbic encephalitis and cerebellar degeneration, though no neoplasm, clinically or pathologically, was detected in this patient. Consequently, it is suggested that when a senile patient presents sub-acute onset of progressive dementia, with a variety of neurological symptoms, paraneoplastic syndrome is to be taken into consideration, even if a tumor or an auto-antibody is not detected since the resection of the tumor is still the best therapeutic means. Otherwise immuno-suppressive and steroid therapies should be used.

DOI： 10.1272/jnms.71.412

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL MUNKSGAARD  

Objective - Progressive supranuclear palsy (PSP) is often misdiagnosed in early phase. The purpose of this study is to investigate the feature of [F-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography images for the early diagnosis of PSP. Methods - We studied 15 patients with PSP and 16 normal subjects. Using SPM99 and analysis of covariance to eliminate the effect of aging, the differences between PSP and normals were displayed as a statistical map. In the PSP, we also investigated the correlation with duration and with the subscores of Unified Parkinson's Disease Rating Scale. Results - The glucose metabolism of midbrain was significantly lower in PSP than in normals. However, correlation was not found between the metabolism of midbrain and clinical deterioration. Conclusions - The statistical map clearly demonstrated the hypometabolism of midbrain in PSP, which is independent of the clinical deterioration. The hypometabolism of midbrain is one of the most promising sign for early diagnosis of PSP.

DOI： 10.1111/j.1600-0404.2004.00293.x

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記述言語：英語   出版者・発行元：(一財)博慈会老人病研究所  

早期発症アルツハイマー病(AD)と晩発型ADは,発症の年齢が最終的な病理学的結果に影響を及ぼすという概念に基づき分類されてきた.早期発症ADと晩発型ADは今やADの1スペクトルとみなされているが,晩発型における新皮質以外の辺縁系の関与のメカニズムはまだ充分に明らかになっていない.この疑問を解明するために,CERAD基準により確認された連続69例のAD患者において発症年齢,死亡年齢,脳重量,疾病期間とBraakステージングとの相関関係をレトロスペクティブに調査した.脳重量と発症年齢とは正の相関関係があったが,疾患期間とは強い負の相関関係があった.神経原線維変化のBraak ステージングを考慮に入れると,高年齢層では数例の例外もあったものの,その傾向は同じであり,疾患の進行は明らかに遅かった.本試験から,ADの高年齢層では,辺縁系を優位とする病理学は,通例,より短時間での臨床経過を示しているにすぎないことが示唆された

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2004&ichushi_jid=J02710&link_issn=&doc_id=20040716320002&doc_link_id=%2Fdh7presy%2F2004%2F001301%2F002%2F0022-0027%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdh7presy%2F2004%2F001301%2F002%2F0022-0027%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In order to clarify the clinical and genetic features of SCA6, we retrospectively analyzed 140 patients. We observed an inverse correlation between the age of onset and the length of the expanded allele, and also between the age of onset and the sum of CAG repeats in the normal and the expanded alleles. The ages of onset of four homozygous patients correlated better with the sum of CAG repeats in both alleles rather than with the expanded allele calculated from heterozygous SCA6 subjects. Clinically, unsteadiness of gait was the main initial symptom, followed by vertigo and oscillopsia, and cerebellar signs were detected in nearly 100% of the patients. In contrast, extracerebellar signs were relatively mild and infrequent. The results of neuro-otological examination performed in 22 patients suggested the purely cerebellar abnormalities of ocular movements in nature. There was a close relationship between downbeat positioning nystagmus (DPN) and positioning vertigo, which became more common in the later stage. We conclude that total number of CAG repeat-units in both alleles is a good parameter for assessment of age of onset in SCA6 including homozygous patients. In addition, clinical and neuro-otological examinations suggested that SCA6 is a disease with predominantly cerebellar dysfunction.

DOI： 10.1007/s10038-004-0142-7

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a 72-year-old woman who died of respitory failure. History included onset of diabetes mellitus at the age of 67 years and hypertension at the age of 72 years. The patient had been in good health otherwise until 2000, when she had onset of numbness or tingling of the bilateral lower limbs. On December 3, 2000, she was admitted to a hospital in the vicinity of her home because of the above-mentioned complaints. Neurological examinations revealed progressive paraplegia. Symptoms and signs suggested Guillain-Barré syndrome. Examinations of cerebrospinal fluids revealed cell count of 338/3 (mono 72%, poly 18%) and protein value of 100 mg/dl. Later the patient course deteriorated. On December 15, 2000, she was admitted to Hakujikai Memorial Hospital for the second time. Ten days later, MRI examination showed diffuse swelling of the spinal cord from the cervical (C 3/4) level to the thoracic level. Gd-enhanced T 1-weighted MRI performed 22 days later showed a partially enhanced lesion at the thoracic (Th 5/6) level of the spinal cord. The patient was treated with steroid therapy (methylprednisolone 500 mg/dl). She died of respiratory failure on January 6, 2001. The patient was presented in a neurological CPC. Neurological and imaging findings suggested a transverse myelopathy. However, there were several points in this case that were unusual for a typical transverse myelopathy, such as total sensory loss below spinal segments of thoracic level (Th 5) and motor weakness of the upper limbs of upper segment of the same level. A clinical neurologist concluded that the patient had subacute transverse myelopathy with fused multiple pathy pathologic lesions. We discussed whether this case was a transverse myelopathy or multiple sclerosis. Post mortem examination revealed acute necrotic myelopathy affecting the spinal cord from the second cervical to the tenth thoracic vertebrae, with conspicuous infiltration of CD 68-positive macrophages involving both gray and white matter, partially necrotic associated with scattered UCHL-1 dominants lymphocytic infiltration of T cells around vessels. There were relatively older lesions with demyelinating features in the spinal roots that were particularly dominant in the anterior roots. No demyelinated plaques in the optic chiasm, tracts and nerves, or in the cerebero-cerebellar white matter were found. Systemic pathological diagnosis was lung edema with fresh hemorrhage, pancreatic atrophy consistent with diabetes mellitus and choleductlithiasis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

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.

DOI： 10.1016/S0022-510X(02)00027-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Alzheimer's disease (AD) and Parkinson's disease share common clinical and pathological features. In this study, we examined the relationship between AD pathology and α-synuclein aggregation. The frequency and distribution of α-synuclein-positive structures were systematically investigated in 27 cases with sporadic AD by α-synuclein immuno-histochemistry. Thirteen (48.2%) of 27 cases had various α-synuclein-positive structures as well as Lewy bodies. The frequency and density of senile plaques and neurofibrillary tangles were not significantly different between cases with α-synuclein structures and those without. α-Synuclein-positive structures were found most frequently in the amygdala. The α-synuclein-positive inclusions that are different from Lewy bodies were observed at the highest rate in the hippocampus. The discovery of α-synuclein as the constituent of Lewy bodies facilitated the detection of Lewy-related structures even in AD cases with widespread and numerous neurofibrillary tangles. α-Synuclein-positive inclusions except for Lewy bodies are exposed, and the distribution of them indicates that Lewy body formation may be influenced by the degree of tau aggregation. This study also supports the suggestion that cases with AD pathology can be classified into two groups according to the existence or absence of α-synuclein aggregation. © 2001 Elsevier Science B.V.

DOI： 10.1016/S0006-8993(00)03082-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Association of Neuropathologists Inc.  

Disease-specific findings in the substantia nigra were examined in cases of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and parkinsonism-dementia complex of Guam (PDC)
diseases in which the patients exhibit dementia and parkinsonism, with neurofibrillary tangles (NFTs) and glial tangles composed of hyperphosphorylated tau. Loss of pigmented neurons was extremely severe in these 3 diseases, and decrease of the nonpigmented neurons was severe in PSP and CBD. On the other hand, in PDC the decrease of the nonpigmented neurons was different in each patient. Topographically, in PSP the nonpigmented neurons were particularly depleted in the ventral part and relative preservation of the pigmented neurons was observed in the medial part at the level examined. Many NFTs were observed in PDC. Although the number of NFTs was small, many pretangles were seen in the neurons in CBD. Granular and hazy astrocytic inclusions were identified exclusively in PDC. Numerous argyrophilic neuropile threads were identified in CBD and PSP, but these were few in PDC. Many foamy spheroid bodies as well as coiled bodies were observed in PSP and CBD, but only a few were observed in PDC. In conclusion, PDC is a disease that is distinctly different from PSP and CBD. It is possible to differentiate between PSP and CBD by the occurrence of many pretangles in CBD, but some similarities between these 2 diseases indicate the existence of common pathological mechanisms.

DOI： 10.1093/jnen/60.4.393

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Different kinds of tau deposits were quantitatively investigated with thiazin red (TR), a fluorochrome that binds to fibrillary structures like neurofibrillary tangles (NFTs), in brains obtained at autopsy from patients with Alzheimer's disease (AD), Pick body (PB) disease, corticobasal degeneration (CBD) or diffuse NFTs with calcification (DNTC). After recording double-labeling fluorescence images with anti-paired helical filament tau (AT8) and TR, the sections were subjected to Gallyas method (GAL). This enabled three different staining properties to be compared on the identical neuron. AT8-positive neocortical neurons of AD and DNTC were fibrillary and uniformly positive for TR and GAL, consistently forming NFTs. NFTs lacking AT8 immunoreactivity (IR) were more frequent in DNTC than in AD, suggesting that evolution of NFTs is more accelerated in DNTC. Scarce TR staining in tau-positive neocortical neurons of CBD suggests their paucity of fibrillary structure. Since the affinity of TR for PB was not consistent, this may be dependent not only on the amount but also the characteristics of fibrillary structures. PBs were further characterized by the scarcity of GAL staining. This approach, which quantitatively clarifies differences between AT8-IR, TR and GAL, provides a morphological basis for further investigations of the different conformational states of tau from its deposition to fibril formation of various types.

DOI： 10.1007/s004010100401

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This is the first report demonstrating that progressive supranuclear palsy (PSP) exists on Guam. This 75-year-old Guamanian Chamorro patient with slight dementia and rigidity with restriction of ocular up gaze was diagnosed as parkinsonism-dementia complex (PDC) of Guam clinically. However, neurofibrillary tangles (NFTs) were scarcely seen in the cerebral cortices and hippocampus, but many NFTs, composed of 15-17 nm straight tubules, were detected in the subthalamic nucleus and brain stem. A large number of tuft-shaped astrocytes were observed in the putamen and motor cortex, and numerous argyrophilic grains were seen in the CA1 and subiculum. These pathological findings are different from those of PDC and consistent with PSP. The present case indicates that PSP and PDC clinically resemble each other, and that precise neuropathological examination is indispensable for the final diagnosis of the patient with parkinsonism, dementia and disturbance of vertical external ocular movement.

DOI： 10.1007/s004010100408

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Double immunofluorescence for paired helical filament (PHF)-tau (AT8) and ubiquitin, enhanced by catalyzed reporter deposition amplification, was combined with thiazin red (TR), a fluorochrome, which has an affinity to fibrillary structures such as neurofibrillary tangles (NFTs). After recording these triple-fluorescent images, sections were subjected to the Gallyas silver impregnation method, so that four different staining properties could be compared on the same structure. Among pyramidal neurons quantified in the hippocampus from six cases of Alzheimer's disease, 60.3% were positive for ubiquitin, and were consistently positive for TR. TR-positive neurons (77.1%) harbored fibrillary structures in the cytoplasm and were always positive for the Gallyas stain, which stained the largest number of legions (94.5%). AT8-positive neurons without fibrillary structure were negative for TR (11.6%, pretangle neurons). Some of the pretangle neurons were positive for the Gallyas stain even without fibrillary structures. Appearance of TR stain and ubiquitin in NFTs, but not in pretangle neurons, suggests that ubiquitin is integrated into tau-positive neurons after their transformation into NFTs. Because TR-positive NFTs sometimes lacked ubiquitin-like immunoreactivity, involvement of ubiquitin may not be an early event during NFT formation. This combined method is now found useful in determining how molecules other than tau are involved during the evolution from tau-positive neurons to NFTs in various neurological disorders characterized by the deposition of tau.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG  

Amplification with catalyzed reporter deposition (CARD) greatly enhances peroxidase signals, which has been utilized to amplify immunohistochemical labelings including fluorochromes. Here we describe a strategy to amplify each of two immunofluorescent signals without crosstalk on double-stained histological sections from human autopsied brains with Alzheimer's disease (AD). One of the two primary antibodies (anti-AP or anti-PHF-tau) was probed by a species-specific secondary antibody conjugated with horseradish peroxidase (HRP), which was visualized by FITC-labeled tyramide. After inactivation of HRP, the other primary antibody was probed by another species-specific secondary antibody conjugated with HRP. Amplification with biotinylated tyramide was followed by streptavidin-conjugated Cy-5, which specifically labeled the latter epitope. It was found that AP and PHF-tau were localized to senile plaques and neurofibrillary tangles (NFTs), respectively, which verified lack of crosstalk on the double-stained section. Localization of ubiquitin and PHF-tau was looked for at higher magnification in NFT-bearing neurons. Although these two epitopes were colocalized in some neurons, ubiquitin was not always present in PHF-tau positive NFTs. Discrepancy between PFH-tau and ubiquitin, verified inter- and intracellularly, may represent different stages of NFT formation. This is the first report of successful CARD amplification of two different fluorescent signals on double-labeling immunohistochemistry, which is now proved to be powerful in detecting epitopes in relation to AD-related lesions. Improved intensity over tenfold of the two fluorescent signals without crosstalk will expand the application of the multilabeling method with fluorochromes.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

The distributions of class III alcohol dehydrogenase (ADH), a glutathione-dependent formaldehyde dehydrogenase, and class I ADH in the human brain were examined immunohistochemically. The most intense immunostaining of class III ADH was observed in the dendrites and cytoplasm of cerebellar Purkinje cells. Scattered cerebral cortical neurons in layers IV and V, and some hippocampal pyramidal neurons were also immunopositive. The neuronal distribution of class III ADH resembled that of the vulnerable neurons in patients with hypoxic encephalopathy, which in view of the intense staining in the Purkinje cells, raises the possibility that this enzyme contributes to the hypoxia and cerebellar degeneration suffered by chronic alcoholics, Perivascular and subependymal astrocytes, which contribute to the maintenance of the cerebral cellular milieu and isolate the brain from the systemic circulation and cerebrospinal fluid, were also class III ADH positive. As the substrates of this enzyme include intrinsic toxic formaldehyde, inflammatory intermediate of 20-hydroxy-leukoteiene B4, and possibly ethanol, the distribution of class III ADH immunostaining indicates this enzyme contributes to the defence of the brain against degenerative processes. The finding that, unlike ependymal cells, subependymal astrocytes were class III ADH positive, suggests this enzyme may be useful for differentiating astrocytes and ependymal cells. (C) 2000 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0006-8993(99)02201-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER VERLAG  

A 58-year-old Chamorro female patient, who died in 1993, was examined clinicopathologically. At the age of 51, she suffered from hemiparkinsonism, then bradykinesia, rigidity without tremor, and dementia. Extrapyramidal symptoms developed, and at the age of 57, vertical gaze palsy was noted. The clinical diagnosis was parkinsonism-dementia complex (PDC) with vertical gaze palsy. The brain showed atrophy in the frontal and temporal lobes, and the atrophy was accentuated in the dentate gyrus, Ammon's horn and parahippocampal gyrus. The basal ganglia, thalamus and midbrain were moderately atrophic. The substantia nigra and locus ceruleus were completely depigmented. Numerous neurofibrillary tangles (NFTs) were seen in the subiculum and amygdaloid nucleus. Many NFTs were evident in the parahippocampal gyrus, lateral occipitotemporal gyrus, insula, Sommer sector, basal nucleus of Meynert, lateral nucleus of the thalamus, subthalamic nucleus and brain stem, and several were observed in the globus pallidus and hypothalamus, The Sommer sector, substantia nigra, locus ceruleus and basal nucleus of Meynert showed severe loss of neurons, and a moderate loss of neurons was exhibited by the globus pallidus. These findings were apparently consistent with those associated with PDC. However, in this patient, severe neuronal loss was seen in the subthalamic nucleus and lateral nucleus of the thalamus, and grumose degeneration, which has not previously been reported in PDC, was seen in the dentate nucleus, In addition, many tufted astrocytes, which have been reported to occur in progressive supranuclear palsy (PSP) and postencephalitic parkinsonism, but scarcely observed in PDC, were present. Furthermore, astrocytic plaques, which have been considered as a specific finding of corticobasal degeneration (CBD), were observed in the cerebral cortex. On the other hand, granular hazy astrocytic inclusions, previously reported to occur in PDC, were not seen. Chromatolytic neurons were not observed. The question thus arises as to whether it is appropriate to consider this patient as having suffered from a combination of PDC, PSP and CBD. From the view points of absence of granular hazy astrocytic inclusions and chromatolytic neurons, and of tufted astrocytes in the neostriatum, it is conceivable that this patient is a case of a new disease entity.

DOI： 10.1007/PL00007410

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Verlag  

Thiazin red (TR), a fluorochrome that has an affinity to fibrillary structures such as neurofibrillary tangles (NFTs) or senile plaques, was utilized to investigate assembly of tau protein into fibrils in tau-immunopositive neocortical neurons of corticobasal degeneration (CBD) and of Alzheimer's disease (AD). Double fluorescence with anti-paired helical filament monoclonal antibody (AT8) and TR was followed by either the Gallyas or Bodian silver impregnation method, which enabled a comparison of the staining features by three different methods on the same neuron. NFTs of AD were uniformly stained by TR and Gallyas method. Most of tau-immunopositive neurons of CBD were similarly stained by Gallyas method but barely or only weakly by TR or Bodian method, suggesting that tau in neocortical neurons of CBD is less liable to form fibrillary structures than in those of AD, easily distinguishable by TR staining. Clarifying the process of tau assembly using this fluorochrome will give a clue to understanding mechanisms of tau deposition, which may be different in various neurological disorders.

DOI： 10.1007/s004010000186

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 67-year-old woman had frequent subacute ileus, hearing difficulty, muscle atrophy and stroke-like episodes. Computed tomography revealed multiple low-density areas, which did not correlate with the vascular supply, in the cerebral cortex. She had metabolic disturbance comprising lactic acidosis and elevated pyruvate level. Her skeletal muscle biopsy specimen showed ragged-red fibers, and mitochondrial DNA analysis revealed a point mutation at position 3243, findings consistent with MELAS. Examination of her small intestine revealed a necrotic zone and numerous abnormal large mitochondria in the smooth muscle cells, vascular media and endothelium, and intestinal ganglion cells. The cerebral cortex showed multiple microcystic necrotic foci in cerebral cortex. Cactus-like pathology resembling the changes associated with Menkes' kinky hair disease and torpedoes were observed in the cerebellar Purkinje cells. The intestinal dysmotility due to MELAS and cerebellar changes were presumed to be associated with a disturbance of copper metabolism.

DOI： 10.1007/s004010000209

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記述言語：英語  

We investigated by immunohistochemistry the deposition of α-synuclein in the brains of deceased patients with the parkinsonism-dementia complex (PDC) of Guam. Five of 13 PDC brains showed numerous α-synuclein positive neuronal inclusions and abnormal neurites, chiefly in the amygdala. Similar α-synuclein positive lesions were observed, although to a lesser extent, in the entorhinal cortex and the dorsal vagal nucleus. No α-synuclein positive inclusions were observed in motor cortex or locus coeruleus, and only a small number of positive inclusions were found in the Sommer's sector, temporal cortex, or substantia nigra. Some of the α-synuclein positive inclusions were reminiscent of cortical Lewy bodies (LB), but many of those in the amygdala coexisted with tau-positive pretangles and/or neurofibrillary tangles (NFT) within the same neurons. In these neurons, tau-positive shells encapsulated α-synuclein positive central cores or irregularly shaped α- synuclein-positive deposition intermingled with pretangles/NFT. Thus, the present study suggests that a common mechanism may govern aggregation of α- synuclein and tau in the amygdala, and that aggregation of α-synuclein may play some role in the neurodegenerative process of a tauopathy (i.e. PDC) in which Aβ deposition is virtually absent.

DOI： 10.1093/jnen/59.7.585

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders  

A case of early cerebral malaria caused by Plasmodium falciparum was studied. P-selectin glycoprotein ligand 1 (PL1) was detected along the inner surface of the infected red blood cells (IRBCs), which ordinarily are not positive for PL1 immunohistochemically, suggesting PL1 being the product of parasite. The electron microscopic finding showed granular deposits in the corresponding lesion, consistent with PL1 deposition, in the IRBCs firmly attached to the endothelium of small cerebral vessels. Most of the IRBCs were round shaped as though they lost their capacity to change shape. The therapeutic strategy was expected against adhesion molecules such as PL1 and for maintaining or restoring the metamorphic capacity of IRBCs. (C) 2000 by W.B. Saunders Company.

DOI： 10.1053/hupa.2000.17996

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER VERLAG  

We present here a case of variant Gerstmann-Straussler syndrome (GSS) with a codon 105 mutation of the prion protein gene. A 57-year-old woman developed dementia and gait disturbance dissimilar to the spastic paraparesis that is observed in most cases with codon 105 mutation. The clinical course of the disease in this case was 12 years. The brain weighed 900 g, and the frontal lobe, pallidum and thalamus were markedly atrophic. Severe neuronal loss was observed in the deep layer of the frontal and temporal cortices, and fibrillary gliosis and a marked loss of neurons was observed in the globus pallidus, thalamus and substantia nigra. Many amyloid plaques and some ballooned neurons were present in the frontal, temporal and parietal cortices. However, no spongiform changes were seen. The cerebellum was relatively well preserved. Numerous neurofibrillary tangles (NFTs) were recognized in the cerebral cortices, and scattered NFTs were observed in the basal nucleus of Meynert, thalamus, substantia nigra, periaqueductal gray matter, raphe nuclei and locus ceruleus. The case presented here indicates the presence of variations in the pathological findings of cases with codon 105 mutation, and that the formation of cortical and brain stem NFTs might have something to do with the duration of illness and/or the degree of brain tissue destruction that had occurred.

DOI： 10.1007/s004010051116

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tissue which has undergone coagulation necrosis (CN) after cerebral infarct is firmer than normal and sharply delimited, and these abnormalities may persist for months or years. This report examines some unusual features, visible on a computed tomography (CT) scan, in two autopsy verified CN cases. In the first case, a ring-shaped enhancement was visible 3 months after the onset of cerebral infarction, which may reflect blood flow in small vessels associated with the collagen capsule. In the second case, a lesion was observed showing hypo-intensity on a T2-weighted image and hyperintensity on a T1-weighted image 4 years after onset. These changes could be attributable to calcium or cholesterin deposition or changes in the collagen capsule. Because CN associated with cerebral infarct is not as rare as previously reported, care should be taken in the interpretation of CT findings which exhibit these features.

DOI： 10.1046/j.1440-1789.1999.00221.x

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記述言語：日本語   出版者・発行元：(有)科学評論社  

47歳男.頸部以下の全身性の発汗低下を主訴とした.44歳時の左脛骨骨折(観血的整復術)後の反射性交感性ジストロフィによると思われる左下肢の自覚的な痺れ感を認めるほか,明らかな異常はなく,検査的にも特に異常はなかった.皮膚生検で観察されたほぼ全ての汗腺周囲に単核球浸潤が認められ,その単核球は全てがCD3陽性であり,T細胞と考えられた.CD4陽性細胞は中等量,CD8陽性細胞は少数であった

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER VERLAG  

Ultrastructural investigation of the hippocampal CA1 and CA4 of nine autopsy-proven cases of dementia of the Alzheimer type (duration of disease: 3-16 years; age: 76-92 years) revealed paired helical filaments (PHFs) and straight tubules (STs) in astrocytes of three advanced cases of long duration (>13 years). The PHFs and STs were indistinguishable from those seen in neurons. The abnormal glial fibrils were confined to the astrocytic processes that were associated with small vessels or, more frequently, with ghost tangles. In both locations the astrocytic PHFs and STs were located in the cytoplasm without limiting membranes, and were thicker than the straight filaments that composed ghost tangles. These findings, combined with the presence of regular constrictions of astrocytic PHFs, suggest that abnormal astrocytic fibers are produced by the glial cells, not engulfed by them. In addition, the presence of these abnormal glial filaments in only advanced, long-duration cases of dementia of the Alzheimer type suggests that disease duration has a significant effect upon the formation of these astrocytic profiles.

DOI： 10.1007/BF00294456

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Coagulation necrosis (CN) – a type of necrosis characterized by firm, eosinophilic parenchyma with recognizable cell outlines – is thought to be a result of rapid degeneration of tissue protein to a gel state and loss of water which prevents the necrotic tissue from undergoing autolysis and cellular digestion. In this study, we observed CN in cerebral infarcts of 11 of 150 consecutive autopsy cases of large cerebral infarction. Cerebral CN in patients who had survived for about 1 month had already started to be surrounded by newly formed vessels and type I collagen-positive tissue. In patients who had survived for more than 1 year, CN was deposited with calcium and cholesterin crystals and encapsulated by thick, dense collagenous tissue. Encapsulation, however, was not always complete, a finding that suggests that other factors, such as gel transformation at an early stage of CN and calcification at a later stage, are important for the persistence of CN in the infarct. The results of our study suggest that cerebral CN occurs more frequently than is generally believed. © 1996, Springer-Verlag Berlin Heidelberg. All rights reserved.

DOI： 10.1007/s004010050391

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記述言語：英語   出版者・発行元：SPRINGER VERLAG  

This report concerns an immunohistochemical and ultrastructural study of cerebral astrocytes in a patient with Pick's disease of 20 years' duration. The autopsied brain was prominently small (710 g) with marked fronto-temporal lobar atrophy. Histological examination demonstrated profound neuronal loss and spongy changes with tau-positive Pick bodies in the frontal and temporal cortex. In addition, many glial cells in the temporal lobe white matter contained round to oval, argentophilic and slightly hematoxinophilic cytoplasmic inclusions that were also immunolabeled with the anti-tau antibody. On electron microscopy, the glial inclusions were observed in the perikarya of astrocytes that were recognized as such from intracytoplasmic glial filaments and the presence of gap junctions. The inclusions were free in the cytoplasm, without a limiting membrane, and mainly comprised irregular aggregations of bundles of about 15-nm straight tubules, which were indistinguishable from those of intraneuronal Pick bodies. Furthermore, various patterns of accumulation of the same straight tubules were frequently noted in perivascular astrocytic processes carrying a basal lamina. These findings indicate that in Pick's disease astrocytes are also affected by a similar insult to that which affects neurons.

DOI： 10.1007/BF00296498

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記述言語：英語  

Progressive muscular dystrophy is characterized by muscle fiber necrosis, regeneration, and endomysial fibrosis. Although absence of dystrophin has been known as the cause of muscle fiber degeneration, pathogenesis of interstitial fibrosis is still unknown. Transforming growth factor-β1 (TGF- β1) induces accumulation of extracellular matrix in various diseases, such as liver cirrhosis and interstitial pneumonitis. To investigate its function on the pathogenesis of progressive muscular dystrophy, it was necessary to determine the degree of TGF-β1 expression and the site of TGF-β1 immunoreactivity. In Duchenne muscular dystrophy and most of Becker muscular dystrophy, high TGF-β1 immunoreactivity expressed on muscle fibers and extracellular space. In other myopathies with endomysial fibrosis, however, TGF-β1 was seldom observed. We also examined the immunoreactivity of the latent TGF-β binding protein, which is bound to the TGF-β precursors. In all Duchenne muscular dystrophy and half of Becker muscular dystrophy cases, high latent TGF-β1 binding protein immunoreactivity was seen, but in other myopathies its immunoreactivity was seldom seen on muscle fibers or extracellular space. Therefore TGF-β1 may play an important role in synthesis and accumulation of extracellular matrix in progressive muscular dystrophy.

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

22歳女,筋および培養線維芽細胞のacid maltase活性は低下していた。抗acid maltase抗体を用いた生検筋のwestern blotで前駆体と考えられる約115kDaのバンドを1本認めたが,正常筋でみられる70kDaのバンドはみられなかった。免疫組織化学では抗acid maltase抗体で筋線維内の空胞が染色された。これらの空胞はacid phosphatase陽性であるのでライソゾームと考えられた。免疫電顕ではライソゾームの内側が標識され,蛋白前駆体は小胞体,ゴルジ装置からライソゾームまで到達していることが示された

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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DOI： 10.3995/jstroke.14.467

CiNii Books

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

37歳男.悪性症候群の治癒後,coenzyme Qおよびidebenoneを投与し,精神異常・痴呆の若干の改善をみた.本症例では生検筋内の小動脈平滑筋細胞内のミトコンドリアに異常があり,MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes)に近い病態があると考えられたが,MELASに高頻度にみられるミトコンドリアDNAの変異はなかった.本例では精神症状が前景にたっていたことから,痴呆の鑑別診断にミトコンドリア脳筋症を候補としてあげるべきと考えた

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

＜Headline＞1 特に初診時は、患者1人ではなく、必ず家族・関係者同伴で診察をする。2 問診では、使用薬剤、日常生活レベルを必ず確認する。3 認知症診断において「治療可能な認知症」を除外することが最も重要である。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01550&link_issn=&doc_id=20210610300010&doc_link_id=10.5692%2Fclinicalneurol.cn-001587&url=https%3A%2F%2Fdoi.org%2F10.5692%2Fclinicalneurol.cn-001587&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

抗N-methyl-D-aspartate(NMDA)受容体脳炎後に発症した薬剤抵抗性てんかんに対し、外科的治療を行い経過が良好であった2例を経験したので報告する。症例は20代の男女で、全身性痙攣を認め入院となり、抗NMDA受容体脳炎と診断され、加療された。退院の後、てんかん発作が薬剤抵抗性となったために緩和的外科的加療を行い、奏功した。抗NMDA受容体脳炎後の症候性てんかんの文献的報告は少ないが、薬剤抵抗性の症例では、外科的治療が選択となり得る。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01550&link_issn=&doc_id=20200116410003&doc_link_id=130007792175&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007792175&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04260&link_issn=&doc_id=20191127430012&doc_link_id=10.1272%2Fmanms.15.220&url=https%3A%2F%2Fdoi.org%2F10.1272%2Fmanms.15.220&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

「認知症を伴う運動ニューロン疾患」(MND-D)は、わが国では湯浅-三山型ALSまたは認知症を伴うALS(ALS-D)と呼称され、欧米に先駆けて臨床病理学的にその検索が進んだ。欧米では、臨床病理学的に前頭側頭型認知症(FTD)の亜型として運動ニューロン疾患型前頭側頭型認知症(FTD-MND)の名称でまとめられ、最近では、TDP-43プロテイノパチーとしてFTDとMND両者の連続性のなかでとらえられている。(著者抄録)

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：英語   出版者・発行元：(一社)日本核医学会  

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記述言語：日本語   出版者・発行元：日本神経感染症学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

認知症の原因で最も多いものはアルツハイマー型認知症で、6〜7割を占める。近時記憶障害と見当識障害で発症し、側頭葉内側面の萎縮が特徴的である。レビー小体型認知症は幻視やパーキンソニズムが特徴的で、近年、DAT-SPECTやMIBG心筋シンチグラフィなどの検査で診断率が向上している。新しい疾患概念である高齢者タウオパチーが決して稀でないことが明らかとなり、鑑別診断上問題となっている。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：臨床体液研究会  

症例は45歳女性で、過睡眠、意識障害で受診し、MRIにて大脳皮質に異常病変を認めた。頭部MRIのFLAIR強調画像で視床、視床下部、脳梁膨大部に高信号領域を認めた。経過などからバソプレシン分泌過剰症(SIADH)による低Na血症を疑った。診断基準に沿って浸透圧や各種ホルモンなどの検査を追加し、診断基準と照合して矛盾しない所見が得られた。MRIにおける中枢性病変と抗AQP4抗体陽性が判明し、SIADHを併発した視神経脊髄炎スペクトラム疾患(NMOsd)と診断した。低Na血症に対する初期治療として高張食塩水の点滴静注を行い、NMOsdの診断後からはステロイドパルス療法を施行した。意識障害は改善したが見当識障害や計算能力の低下などの高次脳機能障害が残存したため、単純血漿交換を施行し、意思疎通が可能な状態にまで回復した。血漿交換後に施行したMRIは入院時と比較して高信号部位の減弱を認めた。

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記述言語：日本語   出版者・発行元：日本自律神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

症例は66歳男性。頭痛・眼痛に続き、複視も出現し入院。左眼に外転麻痺、眼球突出を認め、Tolosa-Hunt症候群を疑いメチルプレドニゾロン1g×3日で加療したが改善無し、造影MRI、髄液、IgG4、ANCAなどは異常を認めず、HbA1c9.2と糖尿病を認めた。発症1週後から、鼻背に帯状疱疹が出現し角膜病変を伴った。眼部帯状疱疹と診断し、アシクロビル15mg/kgを開始、プレドニゾロン1mg/kgから漸減した。眼痛・皮疹は速やかに改善、眼球運動は数ヵ月で徐々に改善した。眼部帯状疱疹で複視が皮疹に先行することは稀である。未治療糖尿病と強力なステロイド治療が、皮疹の出現を抑制していた可能性を推測した。(著者抄録)

DOI： 10.5692/clinicalneurol.cn-000972

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01550&link_issn=&doc_id=20170531270002&doc_link_id=1390001205040478976&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205040478976&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本自律神経学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

74歳女。手指末端の疼痛・潰瘍、下肢筋力の低下、下腿浮腫が出現し、徐々に増悪した。抗signal recognition particle(SRP)抗体が陽性で、筋炎を疑う画像所見から右大腿直筋より筋生検を施行した。単核球の浸潤に乏しく筋線維の壊死像を認め、抗SRP抗体陽性ミオパチーと診断した。また、尿蛋白・尿潜血を認めたため腎生検を施行し、免疫組織化学的にIgA主体の糸球体メサンギウム領域への沈着を認め、メサンギウム増殖性腎炎の組織像を呈しており、IgA腎症と診断した。プレドニゾロン45mg/日内服を開始したところ、筋力は改善し、高値であったCKも低下傾向を示した。しかし、CKの低下が500IU/lでとどまったため、大量ガンマグロブリン静注療法を施行し、その後カルシニューリン阻害薬を併用した。その結果、CKの正常化までに3ヵ月、自力歩行可能までに更に3ヵ月以上を要したが、7ヵ月後に自宅退院した。尿蛋白・潜血も陰性化し、ミオパチーの再燃は認めていない。

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

症例は64歳男性である。発熱・食欲不振・後頸部痛で当院を受診し、髄液検査より細菌性髄膜炎と診断され抗菌薬が投与された。頭部MRIにて多発性脳梗塞が認められ、感染性心内膜炎由来の細菌性髄膜炎を疑い、CefepimeとGentamicinを投与したところ、投与3日後に傾眠傾向を認め、ミオクローヌス・羽ばたき振戦が出現し、脳波では全般性周期放電及び三相波が認められた。非痙攣性てんかん重積との鑑別が困難であったが、Cefepimeの投与を中止したところ速やかに症状改善を認めCefepime脳症と診断した。Cefepime脳症は頻度が高く、腎機能障害・肝機能障害患者および脳梗塞・髄膜炎のような血液脳関門が破壊される病態で起きやすく、注意深く投与すべきだと考えられた。(著者抄録)

DOI： 10.5692/clinicalneurol.cn-000898

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)医学出版  

＜Point＞▼認知症の種類を挙げられる▼アルツハイマー型認知症の症状と臨床経過を説明できる▼レヴィー小体認知症の症状を説明できる▼BPSDに対しての基本的な対応ができる(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

認知症診療の実践におけるコンセンサスを得る目的で、アルツハイマー病研究会に参加した医師を対象として症例を提示して、治療やケアの実地判断について尋ねた。診断や治療、マネジメント等にかかわる種々の判断について、トータライザーを通して回答を得てリアルタイムで表示し、議論した。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)日本医事新報社  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.11.233

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(株)文光堂  

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記述言語：日本語   出版者・発行元：日本画像医学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(有)フジメディカル出版  

進行性核上性麻痺(PSP)やcorticobasal syndrome(CBS)は、運動障害が前景に立つため、主に神経内科医が診療する疾患であるが、パーキンソン病と同様に非運動症状、とくに認知症の重要性が注目され始めている。近時記憶障害や見当識障害が前景に立つアルツハイマー病、幻視が特徴的なレビー小体型認知症や性格変化・反社会的行為が目立つ前頭側頭型認知症と異なり、認知機能障害には際立った特徴がないが、CBSでは進行性非流暢性失語や視空間認知障害、PSPでは自発性の低下や人格変化がみられ、臨床上問題となる。(著者抄録)

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

認知症医療の実践におけるコンセンサスを得る目的で、アルツハイマー病研究会に参加した医師を対象として症例を提示し、認知症医療の実地判断について尋ねた。診断や治療、マネジメント等にかかわる種々の判断についてトータライザーを通して回答を得、そのつどリアルタイムで表示して議論した。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J02464&link_issn=&doc_id=20140404030001&doc_link_id=%2Faj2rsizd%2F2014%2F0025s1%2F002%2F0007-0026%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faj2rsizd%2F2014%2F0025s1%2F002%2F0007-0026%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：エーザイ(株)  

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記述言語：日本語   出版者・発行元：日本神経免疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

完全閉じ込め状態(TLS)の筋萎縮性側索硬化症(ALS)患者(ALS-TLS)と意思疎通をおこなうことを最終的な目的として、どのような感覚がALS-TLSで保たれている可能性があるか、剖検例神経系の種々の感覚経路の保全/障害状態を神経病理学的に検索した。結果は、ALS-TLSでは、視覚路、辺縁系(嗅覚路)などは保たれる傾向を示した。一方、体性感覚路、聴覚路、味覚路などは強く障害されていた。ALS-TLS患者との意思疎通と、意思疎通のためのBMIの開発と使用には、これらの所見を踏まえた入力方法を工夫する必要がある。(著者抄録)

DOI： 10.5692/clinicalneurol.53.1399

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本動脈硬化学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

ARBの大規模臨床研究の結果から、現在日常臨床で用いられているARBでアルツハイマー病の発症進展がある程度抑制できる可能性が示唆され、実験ではアルツハイマー病病理マーカーであるアミロイドβ蛋白やタウとレニン・アンジオテンシン系(RAS)の関係が検討され、RASがアルツハイマー病の病態生理に直接かかわる可能性が示されている。今後はRAS関連薬がアルツハイマー病の治療を視野に入れた新展開を示す可能性もある。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.8.274

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   出版者・発行元：Wiley-Blackwell  

Parkinsonism-dementia complex of Guam is a disease occurring in the Chamorro people of Guam first characterized in clinicopathological studies by Hirano et al. in 1961. Its neuropathological hallmarks are widespread neurofibrillary tangles and neuronal loss, which exhibit a characteristic distribution in cortical and subcortical regions. The neurofibrillary tangles have ultrastructural and biochemical properties similar to those in Alzheimer's disease. Unlike Alzheimer's disease, there are a few neuropil threads and senile plaques and recent studies have also demonstrated that distinct tau-and Gallyas-positive astrocytic inclusions, tau-positive fine granules and massive TDP-43 positive coiled body-like inclusions, reported in parkinsonism-dementia complex, are not found in Alzheimer's disease. © 2011 International Society of Neuropathology.

DOI： 10.1002/9781444341256.ch18

Scopus

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記述言語：日本語   出版者・発行元：(株)南山堂  

＜プライマリ・ケアにおけるポイント＞認知症治療においては、介護者の役割がきわめて大きく、医療者は介護者と良好なコミュニケーションを形成する必要がある。服薬コンプライアンスを向上させるためには、(1)ピルボックス・ケース(カレンダー)の活用、(2)残薬のカウント・内服し終わった包装数のカウントを行う、などして薬剤の投与方法を考え、患者と介護者に対する十分な説明((1)病状・疾患の説明、(2)有害事象の説明、(3)認知症治療薬の説明(効果はどう現れるか))を行う必要がある。また、認知症治療薬の投与用法や剤型も考慮しながら、薬剤選択をすることが重要であり、介護サービスを積極的に利用することも勧めるべきである。(著者抄録)

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(株)日本医事新報社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

高齢者タウオパチーには嗜銀顆粒性認知症、進行性核上性麻痺、神経原線維変化優位型認知症などが含まれる。筆者らは、在宅高齢者対象の総合病院のブレインバンクにおける臨床病理学的な後方視的研究と臨床縦断研究を組み合わせることにより、それら疾患の特徴を明らかにし、早期介入を試みている。とくに嗜銀顆粒性認知症については健忘に加え、特徴的な精神症状を伴うこと、脳の萎縮部位がアルツハイマー病と異なり、左右差を伴って側頭葉内側面の前方優位に目立つこと、髄液バイオマーカーが診断に役立つことが明らかとなった。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)日本医事新報社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

アルツハイマー病(AD)の診断は、近時記憶障害で発症し、見当識障害や失語・失行などの高次機能障害が出現する、という典型的なAD例が示す症状と臨床経過に、頭部MRI(VSRAD)での内嗅野の萎縮、脳血流検査の画像統計解析(eZIS・3D-SSP)での後部帯状回・楔前部の血流低下、PET検査(FDG-PET・アミロイドイメージング)の結果を加えて総合的に行われている。現在も多くのアミロイド仮説に基づく根本治療薬の治験が数多く行われているが、話題を集め注目された有力な治療薬候補がつぎつぎとphase IIIで脱落しており、根本治療薬の開発はけっして容易ではない。対症療法であるアセチルコリンエステラーゼ阻害薬やNMDA受容体拮抗薬の役割はまだまだ重要で、臨床家はこれらの使用方法に十分通じる必要がある。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本頭痛学会  

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記述言語：日本語   出版者・発行元：金原出版(株)  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2011035494

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Web of Science

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記述言語：日本語   出版者・発行元：(株)最新医学社  

グアム島のALS(G-ALS),パーキンソン認知症(PDC)と日本人孤発性ALS,前頭側頭葉変性症,およびそれぞれ対照を神経原線維変化と異常TDP-43から比較した.G-ALSの神経原線維変化の数はPDCより少なく,グアム人対照と同様であった.異常TDP-43蓄積は,前頭葉と歯状回で前頭側頭葉変性症がPDCより著明で,G-ALSは日本人ALSと同様であり,PDCとは局在が異なっていた.(著者抄録)

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2010260806

記述言語：日本語   出版者・発行元：最新医学社  

CiNii Books

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

抗リン酸化αシヌクレイン抗体を用いての免疫組織学的検討が、さまざまな神経疾患において行われ、非シヌクレイノパチーでもαシヌクレインがさまざまな程度に蓄積していることが明らかとなった。非シヌクレイノパチーにおけるαシヌクレイン凝集は、Braakが提唱するレヴィ小体のステージング(出現・進展形式)とは一致しない。また、神経原線維変化(タウ)の出現と密接な関係を有している場合もあり、凝集メカニズムにタウ凝集と共通の背景が存在する可能性も示唆される。(著者抄録)

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

レビー小体型認知症は、アルツハイマー病との鑑別診断上最も重要な変性性認知症疾患である。臨床症状としては動揺する認知機能の障害、早期から出現するパーキンソニズムや幻視に注目することで、また神経画像上は心筋シンチグラフィや脳血流SPECT検査を実施することで、アルツハイマー病との鑑別診断が可能である。前頭側頭型認知症では、新しく蓄積が確認されたTDP-43(TAR DNA-binding protein of 43kDa)とFUS/TLS(fused in sarcoma/translated in liposarcoma)に注目が集まっており、これらの蛋白質をもとにした新しい疾患分類が提唱された。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：日本語   出版者・発行元：(株)にゅーろん社  

著者らのSCUにおけるrt-PAの使用状況と有効性について、使用時期で前半(n=11)と後半(n=11)に分け、比較検討した。その結果、患者の年齢は前半が74±13歳、後半が69±13歳であり、後半で若年の傾向がみられた。慎重投与の有無は前半でありの割合が多い傾向にあった。病型、発症から治療までの平均時間は前半後半ともほぼ同様の結果であった。治療効果は入院時のNIHSSでは後半でやや重症症例が多かったが、24時間後のNIHSSでは後半で有効例が多かった。退院時の有効例(mRS 0-1)は前半18%、後半55%で、死亡例(mRS 6)は前半36%、後半0%であり、後半で治療成績が良かった。この成績はJ-ACT、市販後使用成績調査と比較しても良好な結果であった。累積症例数と使用時期、SCUスタッフ数を検討すると人員の充実に伴って使用ペースも増加していた。尚、いずれの期間も症候性頭蓋内出血は0例であった。

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)新興医学出版社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭痛学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)ライフ・サイエンス  

脳梗塞急性期に対して使用されたクロピドグレルの有用性を後ろ向きに検討した。急性期脳梗塞または一過性脳虚血発作(TIA)で入院し、7日以内にクロピドグレルの投与を開始した、非心原性の脳血管障害患者19例を対象とした。合併症は、高血圧症は19例全員が有し、喫煙の習慣のある症例は8例であった。急性期治療としての静注剤は、オザグレルナトリウムが13例、アルガトロバンが7例に使用された。クロピドグレルは、入院後平均3.1日目に投与された。入院時NIHSSとmRSは有意に改善した。凝固線溶系マーカーと血小板系マーカーは上昇した。白血球数、血小板数、肝機能検査値に異常変動はみられなかった。機能検査値では、ALTで正常範囲内での上昇を認めたが、他の肝酵素値に有意な変動はなかった。クロピドグレルを第一選択薬とした急性期治療は安全であることが示唆された。

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.4.140

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記述言語：日本語   出版者・発行元：(株)中外医学社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.4.67

CiNii Books

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その他リンク： https://jlc.jst.go.jp/DN/JALC/00312961785?from=CiNii

記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.4.4

CiNii Books

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その他リンク： https://jlc.jst.go.jp/DN/JALC/00310716424?from=CiNii

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.3.201

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.3.167

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

35歳初産婦。妊娠経過中に異常を認めなかったが、陣痛発来時に妊娠高血圧症候群の診断で緊急帝王切開を施行した。術後も高血圧が持続し、一過性の意識消失発作と乏尿を認め、溶血・肝機能障害・著明な血小板減少を認めたことからHELLP症候群と診断した。同時に急性腎不全・播種性血管内凝固症候群を合併したため、入院第2、3病日に血漿交換を施行した結果、翌日には意識レベルが改善し、その後血小板・溶血所見の改善を認めた。また、第2病日に施行した頭部MRIで橋・両側尾状核・右被殻外側・左視床にFLAIR/T2で散在性に高信号域を認め、血管原性浮腫と考えられた。グリセオールにより第27病日には高信号域の改善を認め、reversible posterior leukoencephalopathy症候群と診断した。

DOI： 10.2169/naika.96.983

CiNii Books

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その他リンク： https://jlc.jst.go.jp/DN/JALC/00294933534?from=CiNii

記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

症例は47歳時にくも膜下出血の既往がある56歳男性で、浮動性眩暈、歩行障害に続き両側性難聴と耳鳴りが出現し、発症第5病日に入院となった。第6病日の頭部MRI拡散強調像にて両側中小脳脚・両側小脳半球・右大脳脚に高信号病変を認め、第17病日の頭頸部3D-CTアンギオでは両側椎骨動脈の高度狭窄を認めた。治療はオザグレルとグリセロールで開始、翌日には右顔面のしびれ感が出現したためオザグレルをアルガトロバンに変更してエダラボンを併用、第12病日からはシロスタゾールを追加した。聴力は早期から改善傾向を示して日常会話可能となり、難聴以外の神経症状も軽快して第57病日退院となった。第14病日の聴性脳幹反応(ABR)では両側ともII波からV波まで消失していたが、第61病日にはI波からV波まで全波が認められた。ABR所見から難聴の責任病巣は橋下部聴神経線維のほか、蝸牛神経の障害が推定された。以上より本症例は両側椎骨動脈高度狭窄を基盤とした血行力学的機序による脳梗塞で、梗塞部位からの血流が可逆的な聴力変化を来した可能性が示唆された。

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2007060740

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：BLACKWELL PUBLISHING  

Web of Science

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

We examined the autopsied brains of cases of 6 types of tauopathy: parkinsonism-dementia complex of Guam (PDC), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Pick disease, Alzheimer disease (AD), and myotonic dystrophy together with Guamanian controls. Light microscopy sections of these brains were examined using anti-tau antibodies. Tau-positive fine granules (TFGs) were globe-shaped, and 3 to 6 mu m in diameter, were observed predominantly in the frontal white matter in 30 of the 35 patients with PDC. However, no TFGs were found in association with PSP, myotonic dystrophy, Pick disease, AD, or CBD. Western blot analysis of frozen brain tissue taken from the PDC cases revealed that the frontal cortex was hyperphosphorylated and contained 6 tau isoforms (3R + 4R tau). However, in the present study, it was revealed that the novel TFGs in the white matter of patients with PDC was composed of 4R tau. Western blot analysis of sarkosyl-insoluble tau from the white matter of the PDC cases showed 2 major bands of 60 and 64 kDa and one minor band of 67 kDa. After dephosphorylation, these bands resolved into one major band of 4-repeat (4R) tau isoform and 3 minor bands of 3-repeat (3R) and 4R tau isoforms. Moreover, the TFGs observed in cases in which the number of neurofibrillary tangles (NFTs) was higher than the threshold level were not correlated with the presence of cortical NFTs. In conclusion, these novel TFGs were found almost exclusively in PDC brains and could therefore be considered as a characteristic neuropathologic marker of this particular tauopathy. The TFGs were hyperphosphorylated tau-positive structures that may be formed by a different mechanism from that used to produce cortical NFTs.

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本神経感染症学会  

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記述言語：英語   出版者・発行元：日本神経化学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

29歳男.26歳でアジソン病との診断により副腎皮質ホルモン療法を受けていたが,次第に歩行障害と構音障害が進行したため,精査目的で入院となった.小脳性失調,四肢腱反射亢進,病的反射を認め,MRIでは軽度の小脳萎縮および両側小脳歯状核・赤核,橋左側錐体路のT2高信号を認めた.SPECTにて鳥距溝付近の血流量の低下を認め,血漿極長鎖脂肪酸の構成比の異常を認めた.以上から,小脳脳幹型副腎白質ジストロフィーと診断し,経時的にMRIとSPECT所見を追うことができた

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記述言語：日本語   出版者・発行元：(一社)日本頭痛学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

血管性痴呆の多くは脳梗塞によって引き起こされるが,皮質下血管性痴呆では臨床的に脳血管障害が明らかでないことも多く,その診断は厳密な意味では困難かつ不正確である.高齢者ではアルツハイマー病変を合併していることもあり,両者の要素を考慮しなければならず,血管性痴呆は臨床的にも病理学的にも「閾値」を設定することがむずかしい疾患概念である.しかし,血管の変化が一次的であることは間違いなく,高血圧や血圧変動のコントロールなどの危険因子管理などの一次予防が重要である(著者抄録)

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭痛学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSN NEUROPATHOLOGISTS INC  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)ライフ・サイエンス  

暴力行為や性格変化が主な原因で初石病院閉鎖痴呆病床に入院した痴呆患者の特徴を明らかにするため,連続剖検103例の神経病理学的所見を検討した.その結果,当院の場合,最近海外での報告よりも平均年齢が8〜10歳若く,国内の類似報告と比べて血管性痴呆の割合が小さく,アルツハイマー型痴呆(AD)やAD以外の変性性痴呆,たとえばPick病などの比率が高いことが特徴的であった.また,辺縁系に限局してαシヌクレイン陽性構造物凝集がみられる症例が,臨床病理学的に診断された孤発性のADの約1割に認められた.暴力,性格変化,徘徊など,介護上問題となる痴呆症例では,脳梗塞を背景とした血管性痴呆よりも,運動機能障害の少ないADやAD以外の痴呆性神経変性疾患が多いことが示唆された.以上の結果は,当院が介護上問題となる症例を積極的に受入れていることや,長期入院が可能であるため,AD以外の神経変性疾患患者が多く集まっていることが影響していると考えられた

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：医学書院  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2004020130

記述言語：日本語   出版者・発行元：(株)自然科学社  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSN NEUROPATHOLOGISTS INC  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

一般に知的機能は障害されないが,一方で筋萎縮性側索硬化症(ALS)プラス症候群として臨床的に人格変化や社会的異常行動を示す"痴呆を伴うALS(ALS-D)"の存在が注目されている.ALS-Dは一般的には下位運動ニューロン症状が強いという特徴があるが,上位運動ニューロン障害の強い症例もあることから"運動ニューロン疾患を伴う前側頭葉型痴呆"との異同が問題となる.しかし,Bunina小体が存在するなどの点から,ALS-Dの範疇に入ると考えられた.ALS-Dには従来のprototype以外に上位運動ニューロン優位の障害を主徴とした一群"痙縮優位のALS-D"が存在する可能性がある

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2003251469

記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

ビンスワンガ-型痴呆の白質病変形成には細動脈硬化と高血圧症が重要な役割を果たしている.しかし,まだ組織・細胞レベルでの成因に関しては不明な点が多く,更に様々な手法でのアプローチが必要である.今後はこの白質病変部のオリゴデンドログリアがどのようにダメージを受け死に至るのかに焦点をあてて,新しい動物モデルの作製や免疫抑制剤などの新しい観点からの薬物に注目していく必要がある

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)最新医学社  

神経変性疾患における神経細胞死のプロセスから,神経細胞死がネクローシス,アポトーシスのいずれであるかという点を中心にして概説したAlzheimer病や筋萎縮性側索硬化症等の神経変性疾患における神経細胞死が,アポトーシスであるとの報告が相次いでいる.しかし,これらの神経変性疾患ではアポトーシス小体は認められず,細胞変性から死に至る速度もアポトーシスのそれと比較して遥かに遅いと考えられ,アポトーシスとは異なる細胞死のメカニズムが関与している可能性が高いとされている

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Nasu-Hakola disease (NHD) is an autosomal recessive disorder characterized by presenile dementia and bone cysts. Finnish patients revealed a large deletion in DAP12 gene encoding a key element for transducing activation signal. The authors examined six Japanese cases for DAP12 alleles. Five of the six had loss-of-function mutation, either a single-base deletion or a novel point mutation. The single patient without mutation normally expressed DAP12 protein. Japanese NHD has at least three genetic forms regarding DAP12.

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