Neuropathology : official journal of the Japanese Society of Neuropathology
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Up to February 2008, a total of 132 patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been identified in Japan, accounting for a majority of the world's patients with dCJD. The patients received dura mater grafts from 1978 to 1993. Lyodura (B. ⋯ The plaque type accounted for one-third of the pathologically confirmed or clinically diagnosed cases of dCJD. The non-plaque type was associated with methionine homozygosity at codon 129 (129M/M) of the PrP gene in all patients, except for in one patient with the 129M/valine (V) genotype and type 1 protease-resistant PrP (PrP(res)), whereas the plaque type was always associated with the 129M/M genotype and the intermediate type between types 1 and 2 of PrP(res) in all cases. Thus, the clinicopathological and molecular features of the plaque type are distinct from those of the non-plaque type, suggesting contamination of the dura mater grafts with different prion strains.
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Initially, trans activation responsive region (TAR)-DNA-binding protein 43 (TDP-43) was considered to be a disease-specific component of ubiquitin-positive and tau-negative inclusions in the brains of patients with frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS); however, it is now widely known that this protein also abnormally accumulates in neurons in other neurodegenerative diseases. On the basis of observation mainly in the medial temporal lobe, TDP-43-immunoreactive neuronal inclusions have been detected in 20-30% of Alzheimer disease (AD) brains. However, it is controversial whether these cases represent a combined disease, that is, mixed AD/FTLD-U. ⋯ Our findings suggest that abnormal TDP-43 deposition and AD pathology (formation of senile plaques and neurofibrillary tangles) might occur independently. However, taken together with the results of previous reports, the distribution of TDP-43 immunoreactivity in the hippocampus and frontal cortex in AD appear to be varying. We consider that it is still too early to determine that the TDP-43 accumulation is a part of AD pathology or result from a completely independent pathology.
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J1-31 is one of the astrocytic proteins, the expression of which has not been evaluated in astrocytomas. In the present study, we studied the expression of J1-31 protein in astrocytes and astrocytomas in comparison with GFAP, p53 and Ki-67. Materials consisted of formalin-fixed paraffin-embedded tissue specimens that included five cases of normal brain, 17 of gliosis, 15 of pilocytic astrocytoma (WHO grade I), 26 of low-grade diffuse astrocytoma (WHO grade II), four of anaplastic astrocytoma (WHO grade III), and eight of glioblastoma (WHO grade IV). ⋯ In conclusion, down-regulation of J1-31 expression correlates with advancing grade of astrocytomas. The result suggests this protein plays some role in astrocytes that is progressively lost in malignant progression. The anti-J1-31 antibody may help further our understanding of astrocytes in disease and may be useful as an aid in the pathologic diagnosis of astrocytic lesions.
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Insulin-like growth factor-I (IGF-I) is a potent survival factor for motor neurons in animals, and glycogen synthase kinase-3beta (GSK-3beta) is suspected to play roles in apoptosis and tau phosphorylation. Here we report the immunological expression of IGF-I, GSK-3beta, phosphorylated-GSK-3alpha/beta (p-GSK-3alpha/beta) and phosphorylated-tau in the spinal cord and hippocampus of Kii and Guam amyotrophic lateral sclerosis (ALS) patients. Sixteen ALS patients (10 Japanese sporadic, 3 Kii and 3 Guam ALS) and 14 neurological controls (10 Japanese and 4 Guamanian) were examined. ⋯ This suggested that the IGF-I signaling pathway in Guam and Kii ALS patients might function to phosphorylate GSK-3beta to protect neurons from ALS degeneration. Neurofibrillary tangles (NFTs) in the hippocampus and spinal cord from Kii and Guam ALS patients showed the co-localization of PHF-tau and p-GSK-3alpha/beta by a confocal laser scanning technique. The predominant expression of p-GSK-3alpha/beta compared to GSK-3beta in spinal motor neurons and the co-localization of p-GSK-3alpha/beta and PHF-tau in NFT-laden neurons in the hippocampus and spinal cord were characteristic findings of Kii and Guam ALS patients.