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61.
Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice 总被引:4,自引:0,他引:4
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Ikeda M Shoji M Kawarai T Kawarabayashi T Matsubara E Murakami T Sasaki A Tomidokoro Y Ikarashi Y Kuribara H Ishiguro K Hasegawa M Yen SH Chishti MA Harigaya Y Abe K Okamoto K St George-Hyslop P Westaway D 《The American journal of pathology》2005,166(2):521-531
Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3beta and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD). 相似文献
62.
Preparation of Recombinant Human Monoclonal
Antibody Fab Fragments Specific for Entamoeba
histolytica
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Chronic active Epstein-Barr virus (EBV) infection has been recognized as clonal non-neoplastic lymphoproliferative diseases. However, some reports of cases with a multiphenotypic expansion of EBV-infected lymphocytes give rise to questions of how EBV infects multiphenotypic lymphocytes and whether chronic active EBV infection is a truly monoclonal lymphoproliferative disease. We report two patients with chronic active EBV infection who showed expansion of multiphenotypic EBV-infected lymphocytes. EBV DNA was detected in CD4+ and CD8+ T cells and in B cells from pleural fluid of one patient and in T and B cells from a cervical lymph node of the other patient by polymerase chain reaction (PCR). Although real-time PCR showed that there were equally high loads of EBV genomes in CD4+ and CD8+ T cells from the pleural fluid, Southern blot hybridization with terminal repeats of the EBV genome showed a single band of the same molecular weight in three tissue samples from the patient. The results indicated biphenotypic expansions of CD4+ and CD8+ T cells infected with the same clone of EBV. Furthermore, bisulfite PCR analysis showed hypermethylated status in the Cp region in the two patients regardless of their cell populations. There has been a discrepancy between clonality and expansion of multiphenotypic EBV-infected lymphocytes. We speculate that lymphoid progenitor cells that have not differentiated into T and B cell progenitors are infected with EBV, resulting in clonal expansion of EBV-infected multiphenotypic cells. 相似文献
66.
Kousuke Marutsuka Yoshihiro Hasui Yujiro Asada Seiji Naito Yukio Osada Akinobu Sumiyoshi 《Clinical & experimental metastasis》1995,13(2):116-122
Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 µg/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 µg/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis. 相似文献
67.
R. Tateishi K. Taniguchi T. Horai T. Iwanaga H. Taniguchi T. Kabuto M. Sano S. Ishiguro A. Wada 《Virchows Archiv : an international journal of pathology》1976,371(4):283-294
Summary In a series of 79 cases of primary esophageal carcinoma resected at The Center for Adult Diseases, Osaka, there were six tumors with specific histopathologic features valid for the diagnosis of argyrophil cell carcinoma. Of the 6 tumors, 3 were studied electron microscopically and assay for ACTH content was performed on 4 tumors.Clinically, the ages of the 6 patients ranged from 56 to 71 years; two were women and four men. Four of the 6 patients died with widespread tumor recurrences within 9 months of operation.Microscopically, the 6 tumors were composed largely or almost entirely of small, spindle-shaped cells resembling those of oat cell carcinoma of the lung, and were characterized by the arrangement of tumor cells in solid sheets or anastomosing cords, the presence of argyrophil tumor cells, and the deposits of amyloid. Electron microscopically, the three tumors contained neurosecretory-type granules. Using bioassay or radioimmunoassay ACTH activity in the tumor tissues was detected in 3 out of the 4 tumors determined.From the light and electron microscopic characteristics and the assay evidence, it seems reasonable to conclude that the 6 tumors are endocrine polypeptide producing tumors (apudomas) that arise from argyrophil cells normally found among the basal cells of the esophageal mucosa, and that they represent a distinct histopathologic entity clearly distinguishable from other types of esophageal carcinomas.Supported in part by a Grant-in Aid for Cancer Research from the Ministry of Education, Science and Culture, and the Ministry of Health and Welfare, JapanThe authors are grateful to Prof. H. Imura and Dr. Y. Hirate, Department of Internal Medicine, Kobe University School of Medicine for their interest and performing the assays for ACTH on the tumor tissues. 相似文献
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69.
Kazuko Sukegawa Shunji Tomatsu Toshiyuki Fukao Hideki Iwata Xiang-Qian Song Yukiji Yamada Seiji Fukuda Kouji Isogai Tadao Orii 《Human mutation》1995,6(2):136-143
Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical phenotypes of this disease have been described. To identify mutations in individual patients and to examine possible correlations between mutations and clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese patients with different clinical phenotypes. Five missense mutations, S333L (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild), were identified by the RT-PCR method. Transient expression in the enzyme-deficient fibroblasts revealed that all five missense mutant enzymes were synthesized as the normal-size precursor (73 kD), and the nonsense mutant enzymes were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD), although stable mature enzymes (45–56 kD) were not detected by Western blot analysis. Further more, expression of the eight mutant cDNAs resulted in severe reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal cDNA. © 1995 Wiley-Liss, Inc. 相似文献
70.
Saito S Matsui T Kobayashi N Wakisaka H Mominoki K Matsuda S Taniguchi K 《Anatomy and embryology》2003,206(5):349-356
Expression patterns of glycoconjugates were examined by lectin histochemistry in the nasal cavity of the Japanese red-bellied newt, Cynops pyrrhogaster. Its nasal cavity consisted of two components, a flattened chamber, which was the main nasal chamber (MNC), and a lateral diverticulum called the lateral nasal sinus (LNS), which communicated medially with the MNC. The MNC was lined with the olfactory epithelium (OE), while the diverticulum constituting the LNS was lined with the vomeronasal epithelium (VNE). Nasal glands were observed beneath the OE but not beneath the VNE. In addition, a secretory epithelium was revealed on the dorsal boundary between the MNC and the LNS, which we refer to as the boundary secretory epithelium (BSE) in this study. The BSE seemed to play an important role in the construction of the mucous composition of the VNE. Among 21 lectins used in this study, DBA, SBA and Jacalin showed different staining patterns between the OE and the VNE. DBA staining showed remarkable differences between the OE and the VNE; there was intense staining in the free border and the supporting cells of the VNE, whereas there was no staining or weak staining in the cells of the OE. SBA and Jacalin showed different stainings in the receptor neurons for the OE and the VNE. Furthermore, UEA-I and Con A showed different stainings for the nasal glands. UEA-I showed intense staining in the BSE and in the nasal glands located in the ventral wall of the MNC (VNG), whereas Con A showed intense staining in the BSE and in the nasal glands located in the dorsal and medial wall of the MNC (DMNG). The DMNG were observed to send their excretory ducts into the OE, whereas no excretory ducts were observed from the VNG to the OE or the VNE. These results suggested that the secretion by the supporting cells as well as the BSE and the DMNG establishes that there are heterogeneous mucous environments in the OE and the VNE, although both epithelia are situated in the same nasal cavity. 相似文献