| 1. |
Hiroyuki Honda, Kosuke Matsuzono, Kota Satoh, Masayoshi Fujisawa, Satoshi O Suzuki, Chiaki Furuyama, Tetsuyuki Kitamoto, Shigeru Fujimoto, Koji Abe, Toru Iwaki, Detection of cutaneous prion protein deposits could help diagnose GPI-anchorless prion disease with neuropathy., European journal of neurology, 10.1111/ene.14720, 28, 6, 2133-2137, 2021.06, BACKGROUND AND PURPOSE: To investigate prion protein (PrP) deposits in cutaneous tissues of patients of glycosylphosphatidylinositol (GPI)-anchorless prion diseases with neuropathy. METHODS: Cutaneous tissue samples from three patients with GPI-anchorless prion diseases were obtained, two cutaneous biopsy samples from the lower leg of Case 1 (Y162X) and Case 3 (D178fs25), and a cutaneous sample taken from the abdomen during an autopsy of Case 2 (D178fs25). We performed immunohistochemistry for PrP to look for abnormal PrP deposits. RESULTS: PrP deposits were observed in the dermal papilla, the sweat glands, the hair follicles, the arrector pili muscles, and peripheral nerves of all examined cases of GPI-anchorless prion disease with neuropathy. The abnormal PrP accumulation was frequently localized at the basement membrane, and colocalized with laminin. CONCLUSION: Immunohistochemical detection of PrP in cutaneous samples could be used to definitively diagnose GPI-anchorless PrP disease with neuropathy.. |
| 2. |
Shinichiro Mori, Hiroyuki Honda, Hideomi Hamasaki, Naokazu Sasagasako, Satoshi O Suzuki, Hirokazu Furuya, Takayuki Taniwaki, Toru Iwaki, Transactivation response DNA-binding protein of 43 kDa proteinopathy and lysosomal abnormalities in spastic paraplegia type 11., Neuropathology : official journal of the Japanese Society of Neuropathology, 10.1111/neup.12733, 2021.05, Spastic paraplegia type 11 (SPG11) is the most common autosomal recessive hereditary spastic paraplegia with thinning of the corpus callosum. Spatacsin, a protein encoded by the SPG11 gene, is associated with autophagy. SPG11 patients show spastic paraplegia, intellectual disability, dementia, and parkinsonism. A previous neuropathological analysis of SPG11 cases reported neurodegeneration mimicking amyotrophic lateral sclerosis without transactivation response DNA-binding protein of 43 kDa (TDP-43) deposits and unique sequestosome 1 (SQSTM1)-positive neuronal inclusions. We performed a neuropathological examination of two Japanese patients with complicated spastic paraplegia with thinning of the corpus callosum from different families, and one was genetically diagnosed as having SPG11. Both cases showed diffuse atrophy of the brain and spinal cord. Depigmentation of the substantia nigra was also observed. Immunohistochemistry revealed widespread distribution of areas showing TDP-43 aggregation in the central nervous system. The TDP-43 deposits in the thalamus and substantia nigra especially resembled skein-like inclusions. Unique SQSTM1-positive neuronal inclusions, as previously reported, were widespread in the whole central nervous system as well as the dorsal root ganglia. Double-labeling immunofluorescence of the dorsal root ganglia revealed that the unique, large SQSTM1-positive cytoplasmic inclusions of the ganglion cells were labeled with lysosome-associated membrane protein 1 and lysosome-associated membrane protein 2. This is the first report showing TDP-43 pathology in SPG11. The common neuropathological findings of TDP-43-positive inclusions in both the cases imply a causal connection between the TDP-43 proteinopathy and autophagy dysfunction in SPG11.. |
| 3. |
Hiroyuki Honda, Shinichiro Mori, Akihiro Watanabe, Naokazu Sasagasako, Shoko Sadashima, Trang Đồng, Katsuya Satoh, Noriyuki Nishida, Toru Iwaki, Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt-Jakob disease., Neuropathology : official journal of the Japanese Society of Neuropathology, 10.1111/neup.12717, 41, 2, 152-158, 2021.04, We report the general autopsy findings of abnormal prion protein (PrP) deposits with their seeding activities, as assessed by the real-time quaking-induced conversion (RT-QuIC) method, in a 72-year-old female patient with sporadic Creutzfeldt-Jakob disease (sCJD). At 68 years of age, she presented with gait disturbance and visual disorders. Electroencephalography showed periodic synchronous discharge. Myoclonus was also observed. A genetic test revealed that PRNP codon 129 was methionine/methionine (MM). She died of pneumonia three years and four months after disease onset, and a general autopsy was performed. The brain weighed 650 g and appeared markedly atrophic. Immunohistochemistry for PrP revealed synaptic PrP deposits and coarse PrP deposits in the cerebral cortices, basal ganglia, cerebellum, and brainstem. Western blot analysis identified type 1 proteinase-K-resistant PrP in frontal cortex samples. PrP deposits were also observed in systemic organs, including the femoral nerve, psoas major muscle, abdominal skin, adrenal medulla, zona reticularis of the adrenal gland, islet cells of the pancreas, and thyroid gland. The RT-QuIC method revealed positive seeding activities in all examined organs, including the frontal cortex, femoral nerve, psoas major muscle, scalp, abdominal skin, adrenal gland, pancreas, and thyroid gland. The following 50% seeding dose (SD50 ) values were 9.5 (frontal cortex); 8 ± 0.53 (femoral nerve); 7 ± 0.53 (psoas major muscle); and 7.88 ± 0.17 (scalp). The SD50 values for the adrenal gland, dermis, pancreas, and thyroid gland were 6.12 ± 0.53, 5.25, 4.75, and 4.5, respectively. PrP deposits in general organs may be associated with long-term disease duration. This case indicated the necessity for general autopsies in sCJD cases to establish strict infection control procedures for surgical treatment and to examine certain organs.. |
| 4. |
Motoi Yoshimura, Hiroyuki Honda, Naokazu Sasagasako, Shinichiro Mori, Hideomi Hamasaki, Satoshi O Suzuki, Takashi Ishii, Toshiharu Ninomiya, Jun-Ichi Kira, Toru Iwaki, PCBP2 Is Downregulated in Degenerating Neurons and Rarely Observed in TDP-43-Positive Inclusions in Sporadic Amyotrophic Lateral Sclerosis., Journal of neuropathology and experimental neurology, 10.1093/jnen/nlaa148, 80, 3, 220-228, 2021.02, Various heterogeneous nuclear ribonucleoproteins (hnRNPs) are deposited in pathological inclusions of amyotrophic lateral sclerosis (ALS) and related diseases, such as frontotemporal lobar degeneration (FTLD). Recently, poly (rC)-binding protein 2 (PCBP2, hnRNP-E2), a member of the hnRNP family, was reported to be colocalized with transactivation-responsive DNA-binding protein 43 kDa (TDP-43)-immunopositive inclusions in cases of FTLD-TDP. Here, we used immunohistochemical methods to investigate PCBP1 and PCBP2 expression in the spinal cords of sporadic ALS patients, with special reference to TDP-43-positive inclusions. Thirty autopsy cases of sporadic ALS were examined by immunohistochemistry using antibodies against PCBP1, PCBP2, sequestosome 1 (p62), and TDP-43. In control subjects without neurological disorders, neurons predominantly expressed PCBP2, rather than PCBP1, in their cytoplasm and nuclei. Anterior horn cells of sporadic ALS patients often had various levels of PCBP2 expression, and motor neurons with skein-like inclusions often had reduced or lost cytoplasmic and nuclear PCBP2 staining. Notably, one case with FTLD-TDP subtype B pathology had marked colocalization of TDP-43 and PCBP2 in the cytoplasmic inclusions and dystrophic neurites of the cerebral cortex, hippocampus, and spinal cord. In conclusion, PCBP2 was reduced in anterior horn cells of sporadic ALS, but its occurrence in TDP-43 inclusions was a rare phenomenon.. |
| 5. |
Shoko Sadashima, Hiroyuki Honda, Satoshi O Suzuki, Masahiro Shijo, Shinichi Aishima, Keita Kai, Junichi Kira, Toru Iwaki, Accumulation of Astrocytic Aquaporin 4 and Aquaporin 1 in Prion Protein Plaques., Journal of neuropathology and experimental neurology, 10.1093/jnen/nlaa010, 79, 4, 419-429, 2020.04, Gerstmann-Sträussler-Scheinker (GSS) disease with P102L mutation and familial Creutzfeldt-Jakob disease (CJD) with V180I mutation are 2 major hereditary prion diseases in Japan. GSS and some familial CJD [V180I] exhibit characteristic prion protein (PrP) plaques. Overexpression of the astrocytic water channel proteins aquaporin (AQP) 1 and AQP4 was recently reported in sporadic CJD. To clarify the pathological characteristics of AQP1 and AQP4 in prion disease patient brains with plaque-type deposition, we investigated 5 patients with GSS, 2 patients with CJD [V180I], and 2 age-matched control cases without neurological diseases using immunohistochemistry and double immunofluorescence methods. We demonstrated that there is the intense expression of AQP1 and AQP4 around prion plaques, especially in distal astrocytic processes deep inside these plaques. Similar results have been reported in the senile plaques and ghost tangles of Alzheimer disease brains and a protective role of AQP4 in which AQP4 is redistributed toward the plaques and works as a barrier against the deleterious effects of these plaques has been suggested. Our results, which show a similar clustering of AQPs around PrP plaques, therefore support the possibility that AQPs also have a protective role in plaque formation in prion diseases.. |
| 6. |
Shinichiro Mori, Hiroyuki Honda, Takashi Ishii, Motoi Yoshimura, Naokazu Sasagasako, Satoshi O. Suzuki, Takayuki Taniwaki, Toru Iwaki, Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)-binding protein 1 in Huntington's disease, Neuropathology, 10.1111/neup.12600, 39, 5, 358-367, 2019.10, Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Immunohistochemical studies using the 1C2 antibody for polyglutamine expansion have detected characteristic intranuclear inclusions (INIs) in affected neurons in HD. Further, in vitro and mouse models of HD have shown that the INIs recruit several proteins relating to RNA splicing and translation. In the present study, we immunohistochemically investigated the association of INIs with various heterogeneous nuclear ribonucleoproteins in the cerebral cortex of four autopsy cases of HD. Fused in sarcoma (FUS) was colocalized with 1C2-positive nuclear inclusions in all examined cases. Localization of poly (rC)-binding protein 1 (PCBP1) in 1C2-positive nuclear inclusions was also observed. Double immunofluorescence revealed complete or partial loss of the normal, diffuse nuclear distribution of FUS or PCBP1 in neurons with 1C2-positive nuclear inclusions. This maldistribution of FUS in cortical neurons suggests a severe disturbance of messenger RNA processing, which may be a common pathogenetic mechanism of FUS-related familial amyotrophic lateral sclerosis.. |
| 7. |
Hiroyuki Honda, Masaki Matsumoto, Masahiro Shijo, Hideomi Hamasaki, Shoko Sadashima, Satoshi O. Suzuki, Shinichi Aishima, Keita Kai, Keiichi I. Nakayama, Naokazu Sasagasako, Toru Iwaki, Frequent Detection of Pituitary-Derived PrPres in Human Prion Diseases, Journal of Neuropathology and Experimental Neurology, 10.1093/jnen/nlz075, 78, 10, 922-929, 2019.10, Human prion diseases including sporadic Creutzfeldt-Jakob disease (sCJD), inherited prion diseases, and acquired human prion diseases are lethal neurodegenerative diseases. One of the major sources of iatrogenic Creutzfeldt-Jakob disease was human growth hormone (hGH-iCJD) derived from contaminated cadaveric pituitaries. The incidence of hGH-iCJD has decreased since changing from growth hormone extracted from human cadaveric pituitaries to recombinant pituitary hormones. However, extensive analysis on the localization and detecting of abnormal prion protein in the pituitary gland are limited. In this study, we examined 9 autopsied brains and pituitary glands from 6 patients with prion disease (3 Gerstmann-Sträussler-Scheinker disease, 2 sCJD, and 1 dura mater graft-associated CJD) and 3 individuals with nonprion diseases. Western blot analysis of pituitary samples demonstrated unique glycoforms of normal cellular prion protein with molecular weights of 30-40 kDa, which was higher than the typical 25-35 kDa prion protein in brains. Proteomic analysis also revealed prion protein approximately the molecular weight of 40 kDa in pituitary samples. Moreover, proteinase K-resistant Prion protein was frequently detected in pituitary samples of the prion diseases. Immunohistochemistry for Prion protein revealed mosaic cellular distribution preferentially in growth hormone- or prolactin-producing cells.. |
| 8. |
Masahiro Shijo, Hideomi Hamasaki, Hiroyuki Honda, Satoshi O. Suzuki, Masaki Tachibana, Tetsuro Ago, Takanari Kitazono, Koji Iihara, Toru Iwaki, Upregulation of Annexin A1 in Reactive Astrocytes and Its Subtle Induction in Microglia at the Boundaries of Human Brain Infarcts, Journal of Neuropathology and Experimental Neurology, 10.1093/jnen/nlz079, 78, 10, 961-970, 2019.10, Annexin A1 (ANXA1) has multiple functions, including anti-inflammatory effects, and is thought to be neuroprotective in various pathophysiologies of the central nervous system. The importance of ANXA1 in microglia and endothelial cells in ischemic environments in the brain has been recognized, but its detailed behavior in astrocytes in the ischemic brain remains unknown. Using immunohistochemistry, we therefore assessed the altered distribution of ANXA1 in human brain infarcts using 14 autopsied samples and 18 surgical samples. Elevated expression of ANXA1 was observed in reactive astrocytes in peri-infarct regions. ANXA1 accumulated at the cell periphery and in swollen cytoplasmic processes of reactive astrocytes, as well as at the rim of vacuoles at the boundary of necrosis, and colocalized with aberrantly distributed aquaporin 4 and excitatory amino acid transporter 1. Foamy macrophages in the necrotic core also expressed abundant ANXA1, whereas resident microglia at the boundary of necrosis rarely showed intrinsic expression of ANXA1. This characteristic distribution of ANXA1 in human brain infarcts may represent the good adaptability of reactive astrocytes to ischemic damage.. |
| 9. |
Hamasaki H, Honda H, Suzuki SO, Shijo M, Ohara T, Hatabe Y, Okamoto T, Ninomiya T, Iwaki T, Tauopathy in basal ganglia involvement is exacerbated in a subset of patients with Alzheimer's disease: The Hisayama study., Alzheimer's & dementia (Amsterdam, Netherlands), 10.1016/j.dadm.2019.04.008, 11, 415-423, 2019.06. |
| 10. |
Shijo M, Honda H, Suzuki SO, Hamasaki H, Hokama M, Abolhassani N, Nakabeppu Y, Ninomiya T, Kitazono T, Iwaki T., Association of adipocyte enhancer-binding protein 1 with Alzheimer's disease pathology in human hippocampi, Brain Pathol., 10.1111/bpa.12475, 28, 1, 58-71, 2019.01, Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes. Up-regulation of AEBP1 in the hippocampi of patients with Alzheimer's disease (AD) has been revealed by microarray analyses of autopsied brains from the Japanese general population (the Hisayama study). In this study, we compared the expression patterns of AEBP1 in normal and AD brains, including in the hippocampus, using immunohistochemistry. The subjects were 24 AD cases and 52 non-AD cases. Brain specimens were immunostained with antibodies against AEBP1, tau protein, amyloid β protein, NF-κB, GFAP and Iba-1. In normal brains, AEBP1 immunoreactivity mainly localized to the perikarya of hippocampal pyramidal neurons, and its expression was elevated in the pyramidal neurons and some astrocytes in AD hippocampi. Although AEBP1 immunoreactivity was almost absent in neurons containing neurofibrillary tangles, AEBP1 was highly expressed in neurons with pretangles and in the tau-immunopositive, dystrophic neurites of senile plaques. Nuclear localization of NF-κB was also observed in certain AEBP1-positive neurons in AD cases. Comparison of AD and non-AD cases suggested a positive correlation between the expression level of AEBP1 and the degree of amyloid β pathology. These findings imply that AEBP1 protein has a role in the progression of AD pathology.. |
| 11. |
Norihisa Maeda, Hiroyuki Honda, Satoshi Suzuki, Naoki Fujii, Jun-Ichi Kira, Toru Iwaki, Mitochondrial dysfunction and altered ribostasis in hippocampal neurons with cytoplasmic inclusions of multiple system atrophy, Neuropathology, 10.1111/neup.12482, 38, 4, 361-371, 2018.08, Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disease. It has recently been shown that patients with MSA accompanied by cognitive decline display numerous neuronal cytoplasmic inclusions (NCIs) in the limbic neurons. We examined potential mechanisms underlying the formation of these NCIs by determining of mitochondrial function and statuses of RNA processing by analyzing 12 pathologically confirmed cases of MSA. Among them, four had cognitive impairment Semiquantitative evaluation using immunohistochemistry analyses revealed a significantly greater NCI burden in the hippocampal cornu ammonis 1 (CA1) subfield, subiculum, and amygdala in the cases with cognitive impairments compared with those without cognitive impairment. Immunofluorescent staining revealed that limbic neurons with NCIs often accelerated production of reactive oxygen species (ROS) and degraded mitochondrial quality control. Immunofluorescent staining also revealed that neurons with these NCIs translocated heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) from the nucleus and aggregated abnormally at the perinuclear rim. Since the NCIs in the hippocampal neurons of MSA with cognitive impairments were more numerous, the neuronal mitochondrial dysfunction and altered ribostasis observed in NCI formation may be involved in the hippocampal degeneration of MSA.. |
| 12. |
Hiroyuki Honda, Naokazu Sasagasako, Chang Shen, Masahiro Shijo, Hideomi Hamasaki, Satoshi O. Suzuki, Yoshio Tsuboi, Naoki Fujii, Toru Iwaki, DCTN1 F52L mutation case of Perry syndrome with progressive supranuclear palsy-like tauopathy, Parkinsonism and Related Disorders, 10.1016/j.parkreldis.2018.02.038, 51, 105-110, Epub ahead of print, 2018.06, Introduction: Perry syndrome is a rapidly progressive, autosomal dominant parkinsonism characterized by central hypoventilation, depression and severe weight loss. To date, eight DCTN1 mutations have been identified associated with Perry syndrome. A novel F52L DCTN1 mutation case of Perry syndrome is characterized by late-onset parkinsonism and frontotemporal atrophy. Methods: A Japanese woman suffered from slowly progressing parkinsonism since age 48. At age 59, she developed central hypoventilation, and required breathing assistance. Gene analysis identified a p.F52L mutation in DCTN1 and she was diagnosed with Perry syndrome. She died of aspiration pneumonia at age 74. Results: Postmortem examination revealed severe neuronal loss in the substantia nigra and the putamen. Immunohistochemistry for DCTN1 revealed many abnormal aggregates, mainly in neurons in the brainstem and basal ganglia. Additionally, numerous abnormal phosphorylated tau deposits including neurofibrillary tangles, tuft-shaped astrocytes and coiled bodies were observed mainly in the basal ganglia, brainstem and cerebellum. These correspond with the neuropathologic criteria for progressive supranuclear palsy. Colocalization of DCTN1 and tau were occasionally seen. Colocalization of phosphorylated α-synuclein and DCTN1 were also observed in Lewy body-like structures in oculomotor nuclei. Phosphorylated TARDBP-positive neuronal cytoplasmic inclusions were few. Conclusion: In conjunction with long disease duration and aging, our findings suggest that the F52L DCTN1 mutation may evoke severe tauopathy and moderate α-synucleinopathy.. |
| 13. |
Chang Shen, Hiroyuki Honda, Satoshi Suzuki, Norihisa Maeda, Masahiro Shijo, Hideomi Hamasaki, Naokazu Sasagasako, Naoki Fujii, Toru Iwaki, Dynactin is involved in Lewy body pathology, Neuropathology, 10.1111/neup.12512, 38, 6, 583-590, 2018.02, Dynactin forms a protein complex with dynein that retrogradely transports cargo along microtubules. Dysfunction of this dynein-dynactin complex causes several neurodegenerative diseases such as Perry syndrome, motor neuron diseases and progressive supranuclear palsy. Recently, we reported colocalization of phosphorylated α-synuclein (p-SNCA) and the largest subunit of dynactin (DCTN1) in Lewy body (LB)-like structures in Perry syndrome. Previous reports have not focused on the relationship between dynactin and synucleinopathies. Thus, we examined autopsied human brains from patients with Parkinson's disease, dementia with LBs, and multiple system atrophy using immunohistochemistry for p-SNCA, DCTN1, dynactin 2 (DCTN2, dynamitin) and dynein cytoplasmic 1 intermediate chain 1 (DYNC1I1). We also examined microtubule affinity-regulating kinases (MARKs), which phosphorylate microtubule-associated proteins and trigger microtubule disruption. Both brainstem-type and cortical LBs were immunopositive for DCTN1, DCTN2, DYNC1I1 and p-MARK and their staining often overlapped with p-SNCA. Lewy neurites were also immunopositive for DCTN1, DCTN2 and DYNC1I1. However, p-SNCA-positive inclusions of multiple system atrophy, which included both glial and neuronal cytoplasmic inclusions, were immunonegative for DCTN1, DCTN2, DYNC1I1 and p-MARK. Thus, immunohistochemistry for dynein-dynactin complex molecules, especially DCTN1, can clearly distinguish LBs from neuronal cytoplasmic inclusions. Our results suggest that dynactin is closely associated with LB pathology.. |
| 14. |
Matsuzaki T, Sasaki K, Tanizaki Y, Hata J, Fujimi K, Matsui Y, Sekita A, Suzuki SO, Kanba S, Kiyohara Y, Iwaki T, Insulin resistance is associated with the pathology of Alzheimer’s disease: the Hisayama Study., Neurology, 10.1212/WNL.0b013e3181eee25f, 75, 9, 764-770, Epub 2010 Aug 25., 2010.08, タイトル：インスリン抵抗性はアルツハイマー病の脳病理と関連する
目的：我々は、糖尿病がAlzheimer病（AD）の病理学的過程にどのように影響を与えるのかについて評価するために、糖尿病関連因子とAD病理との関連について検討を行った。
方法：この研究では、福岡県久山町の住民のうち、1998年から2003年までに死亡し、かつ1988年の検診にて75g経口血糖負荷試験を施行された連続剖検135名（男性74名、女性61名）の検体を用いた。我々は、1988年の検診において、糖尿病関連因子として、空腹時血糖、糖負荷2時間後血糖、空腹時インスリン、インスリン抵抗性評価尺度（HOMA-IR）を測定した。脳内の老人斑についてはCERADガイドライン、神経原線維変化についてはBraakステージ分類に基づいて評価した。各因子とAD病理との関連についての解析は、共分散分析とロジスティック解析を行った。
結果：解析にて、性、年齢、収縮期血圧、総コレステロール、BMI、喫煙、運動、脳血管障害で調整すると、糖負荷2時間後血糖、空腹時インスリン、HOMA-IRの高値が、老人斑のリスクの上昇と関連した。しかし、糖尿病関連因子と神経原線維変化については、有意な関連を認めなかった。AD病理のリスクに関して、アポリポ蛋白E（APOE）の遺伝子型を考慮すると、高血糖とAPOEε4が共存すると、老人斑形成のリスクが上がった。同様の傾向は、高インスリン血症やHOMA-IR高値でも認められた。
結論：この研究から、インスリン抵抗性によって引き起こされる高インスリン血症、高血糖が、APOEε4とともに、老人斑形成を加速させることが示唆された。
Objective: We examined the association between diabetes-related factors and pathology of Alzheimer disease (AD) to evaluate how diabetes affects the pathogenic process of AD.
Methods: This study included specimens from a series of 135 autopsies of residents of the town of Hisayama in Fukuoka prefecture (74 men and 61 women) performed between 1998 and 2003, who underwent a 75-g oral glucose tolerance test in clinical examinations in 1988. We measured diabetes-related factors including fasting glucose, 2-hour post-load plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 1988. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines and neurofibrillary tangles (NFTs) were assessed according to Braak stage. The associations between each factor and AD pathology were examined by analysis of covariance and logistic regression analyses.
Results: Higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were associated with increased risk for NPs after adjustment for age, sex, systolic blood pressure, total cholesterol, body mass index, habitual smoking, regular exercise, and cerebrovascular disease. However, there were no relationships between diabetes-related factors and NFTs. Regarding the effects of APOE genotype on the risk of AD pathology, the coexistence of hyperglycemia and APOE epsilon 4 increased the risk for NP formation. A similar enhancement was observed for hyperinsulinemia and high HOMA-IR.
Conclusion: The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE epsilon 4.. |
| 15. |
Fujii N, Furuta A, Yamaguchi H, Nakanishi K, Iwaki T., Limbic encephalitis associated with recurrent thymoma: A postmortem study, Neurology, 57, 2, 344-347, 57:344-347, 2001.01. |
| 16. |
Suzuki SO, Mizoguchi M, Iwaki T, Detection of SV40 T antigen genome in human gliomas., Brain Tumor Pathol., 14: 125-129, 1997.01. |
| 17. |
Suzuki SO, Iwaki T, Kitamoto T, Fukui M, Tateishi J, Differential expression of CD44 variants among meningioma subtypes., J. Clin. Pathol: Clin. Mol. Pathol., 49, 3, M140-M146, 49: M140-M146, 1996., 1996.01. |
| 18. |
Hitotsumatsu T, Iwaki T, Fukui, M, Tateishi J, Distinctive immunohistochemical profiles of small heat shock proteins (heat shock protein 27 and alphaB-crystallin) in human brain tumors., Cancer, 10.1002/(SICI)1097-0142(19960115)77:2<352::AID-CNCR19>3.0.CO;2-0, 77, 2, 352-361, 77: 352-361, 1996.01.  |
| 19. |
Masaru Ohta, Tom Iwaki, Tetsuyuki Kitamoto, Iwao Takeshita, Jun Tateishi, Masashi Fukui, MIB1 staining index and scoring of histologic features in meningioma. Indicators for the prediction of biologic potential and postoperative management, Cancer, 10.1002/1097-0142(19941215)74:12<3176::aid-cncr2820741217>3.0.co;2-n, 74, 12, 3176-3189, 74: 3176-3189, 1994.12. |
| 20. |
Iwaki T, Wisniewski T, Iwaki A, Corbin E, Tomokane N, Tateishi J, Goldman JE:, Accumulation of alphaB-crystallin in central nervous system glia and neurons in pathologic conditions., Am. J. Pathol., 140, 2, 345-356, 1992.02. |
| 21. |
T Iwaki, A Kume-Iwaki, J E Goldman, Cellular distribution of alpha B-crystallin in non-lenticular tissues., Journal of Histochemistry & Cytochemistry, 10.1177/38.1.2294148, 38, 1, 31-39, 1990.01. |
| 22. |
Iwaki T, Kume-Iwaki A, Liem RKH, Goldman JE, alphaB-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain., Cell, 10.1016/0092-8674(89)90173-6, 57, 1, 71-78, 1989.04, Rosenthal fibers (RFs) are abnormal inclusions within astrocytes, characteristic of Alexander's disease. We have previously isolated a 22 kd protein component of RFs from Alexander's disease brain. By Western blotting, we detected its equivalent in several rat organs, with the highest level in heart, and in a human astrocytoma cell line (U-373MG). A cDNA library established from U-373MG was screened with an anti-RF protein antibody. A partial cDNA clone encoding the lens protein alpha B-crystallin was isolated. The anti-RF protein antibodies react with lens alpha B-crystallin. Furthermore, the distribution of alpha B-crystallin mRNA in rat organs is consistent with the Western blots. Therefore, alpha B-crystallin is not lens-specific and it can accumulate in large amounts in astrocytes in pathological conditions.. |
| 23. |
T. Iwaki, M. Fukui, A. Kondo, T. Matsushima, I. Takeshita, Epithelial properties of pleomorphic xanthoastrocytomas determined in ultrastructural and immunohistochemical studies, Acta Neuropathologica, 10.1007/BF00692844, 74, 2, 142-150, 1987.06, Three cases of pleomorphic xanthoastrocytoma (PXA), one of which showed anaplastic evolution, are described. In all three the PXA tumors were well circumscribed and could be totally removed. Light-microscopically, pleomorphic tumor cells clustered gregariously and often formed alveolar structures. Electron microscopy revealed various epithelial properties, such as junctions and interdigitations between apposing tumor cells, and prominent basal laminae surrounding tumor nests. The circumscribed growth of PXA, as contrasted with an infiltrative growth of usual astrocytoma, can be attributed to the cellular cohesion based on the epithelial properties of the tumor cells. In the third patient, tumor recurred 6 months postoperatively. Although the recurrent tumor retained the alveolar structures, pleomorphism and various degenerative features of the tumor cells diminished with advance in the proliferative activities. © 1987 Springer-Verlag.. |
| 24. |
T. Iwaki, A. Kondo, I. Takeshita, H. Nakagaki, K. Kitamura, J. Tateishi, Proliferating potential of folliculo-stellate cells in human pituitary adenomas - Immunohistochemical and electron microscopic analysis, Acta Neuropathologica, 10.1007/BF00688045, 71, 3-4, 233-242, 1986.09, Folliculo-stellate cells (FS cells) in 40 pituitary adenomas and portions of anterior pituitary adjacent to the tumor in 26 cases were investigated immunohistochemically, using polyclonal antisera to S-100 protein (S-100) and glial fibrillary acidic protein (GFAP). The objective was to clarify the histological behavior of the FS cells. In most pituitary adenomas there were few or no S-100-or GFAP-positive cell, in comparison with numerous positive cells in the parts of the adenohypophyses compressed by adenomas. However, positive FS cells were observed in some types of pituitary adenomas. Growth hormone and prolactin producing adenomas frequently contained significant amounts of FS cells. In non-functioning adenomas, an unique case of FS cell adenoma was present. The adenoma was composed mainly of FS cells and immature glandular cells. The FS cells were sometimes located around follicles containing Periodic acid Schiff-positive material. Therefore, the FS cell adenoma is characterized by S-100- and GFAP-positive FS cells and PAS-positive follicles. In this type of adenoma, FS cells seemed to be the main proliferating component. In parts of the adenohypophyses adjacent to the adenomas, GFAP0-positive FS cells were numerous. In the pathological conditions FS cells may possess the potential of reactive proliferation. © 1986 Springer-Verlag.. |
