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11.
Myopathy phenotype in transgenic mice expressing mutated PABPN1 as a model of oculopharyngeal muscular dystrophy 总被引:1,自引:2,他引:1
Hino H Araki K Uyama E Takeya M Araki M Yoshinobu K Miike K Kawazoe Y Maeda Y Uchino M Yamamura K 《Human molecular genetics》2004,13(2):181-190
Autosomal dominant oculopharyngeal muscular dystrophy (OPMD)is a late-onset disorder characterized clinically by progressiveptosis, dysphagia and limb weakness, and by unique intranuclearinclusions in the skeletal muscle fibers. The disease is causedby the expansion of a 10-alanine stretch to 1217 alanineresidues in the poly(A)-binding protein, nuclear 1 (PABPN1;PABP2). While PABPN1 is a major component of the inclusionsin OPMD, the exact cause of the disease is unknown. To elucidatethe molecular mechanism and to construct a useful model fortherapeutic trials, we have generated transgenic mice expressingthe hPABPN1. Transgenic mice lines expressing a normal hPABPN1with 10-alanine stretch did not reveal myopathic changes, whereaslines expressing high levels of expanded hPABPN1 with a 13-alaninestretch showed an apparent myopathy phenotype, especially inold age. Pathological studies in the latter mice disclosed intranuclearinclusions consisting of aggregated mutant hPABPN1 product.Furthermore, some TUNEL positive nuclei were shown around degeneratingfibers and a cluster of it in the lesion in necrotic musclefibers. Interestingly, the degree of myopathic changes was moreprominent in the eyelid and pharyngeal muscles. Further, muscleweakness in the limbs was apparent as shown by the fatigabilitytest. Nuclear inclusions seemed to develop gradually with aging,at least after 1 week of age, in model mouse muscles. We establishedthe first transgenic mouse model of OPMD by expressing mutatedPABPN1, and our model mice appear to have more dramatic alternationsin myofiber viability. * To whom correspondence should be addressed. Tel: +81 963736083; Fax: +81 963736599; Email: yamamura{at}gpo.kumamoto-u.ac.jp 相似文献
12.
Antigenic Characterization of Hantaan and Seoul Virus Nucleocapsid Proteins Expressed by Recombinant Baculovirus: Application of a Truncated Protein, Lacking an Antigenic Region Common to the Two Viruses, as a Serotyping Antigen 总被引:11,自引:1,他引:11 下载免费PDF全文
Mayuko Morii Kumiko Yoshimatsu Jiro Arikawa Guizen Zhou Hiroaki Kariwa Ikuo Takashima 《Journal of clinical microbiology》1998,36(9):2514-2521
Hantaan virus (HTN) and Seoul virus (SEO) are members of the genus Hantavirus in the family Bunyaviridae and are causative agents of hemorrhagic fever with renal syndrome. The complete and truncated nucleocapsid proteins (NP) of HTN and SEO were expressed by a recombinant baculovirus system. Antigenic characterization of the NP using monoclonal antibodies (MAbs) indicated that the binding sites for the serotype-specific MAbs were located between amino acids (aa) 155 and 429. A Western blot assay indicated that the serotype-specific epitopes were conformation dependent. An indirect immunofluorescence antibody (IFA) assay with the truncated NP (aa 155 to 429) was able to distinguish convalescent-phase sera from HTN and SEO patients. However, the antibody titers with the truncated NP were lower than those with the whole NP. The truncated NP of SEO (aa 155 to 429) could be used as an enzyme-linked immunosorbent assay (ELISA) antigen, but the truncated NP from HTN lost its reactivity when used for ELISA. The IFA assay using baculovirus-expressed truncated NP as an antigen is a rapid, simple, and safe test for distinguishing between HTN and SEO infections by serotype. 相似文献
13.
14.
Hara Masatoshi Tanaka Shigeru Torisu Kumiko Matsukuma Yuta Tsuchimoto Akihiro Tokumoto Masanori Ooboshi Hiroaki Nakano Toshiaki Tsuruya Kazuhiko Kitazono Takanari 《Clinical and experimental nephrology》2021,25(8):822-834
Clinical and Experimental Nephrology - A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis... 相似文献
15.
Reduction of cell proliferative activities of gastric stump adenomatous hyperplasias after bile reflux diversion in rats 总被引:4,自引:1,他引:3
Imai Toshio; Kobayasi Shoiti; Rodrigues Maria Aparecida Marchesan; Camargo Joao Lauro Viana de; Ogawa Kumiko; Iwata Hitoshi; Tatematsu Masae 《Carcinogenesis》1993,14(9):1765-1769
Previously we reported the majority of lesions induced by bilereflux, in the absence of chemical carcinogens, in the rat remnantstomach to consist primarily of gastric type and secondarilyof intestinal type cells, and that they are reversible afterdiversion of bile reflux. The present study was designed toevaluate changes in proliferative activities in cells of eachtype under these conditions. The frequency of adenomatous hyperplasia(AH) induced in the gastric stump mucosa by duodenal contentreflux after Billroth II partial gastrectomy (BII) increaseduntil the 54th week of the experiment. Roux-en-Y (RY) surgicalprocedure which prevents duodenal reflux performed at the 24thor 36th week after BII led to a decrease in AH. Cell contentof the lesions was analyzed using routine H&E staining,immunohistochemical staining for pepsinogen isoenzyme 1 andhistochemical procedures for mucins (paradoxical concanavalinA, galactose oxidase Schiff and sialidase galactose oxidaseSchiff reactions) and proliferation in each compartment evaluatedby an immunohistochemical method using bromodeoxyuridine (BrdU)and a monoclonal antibody against BrdU. At the 54th week thenumber of BrdU-labeled cells per normal pyloric column was significantly(P < 0.05) increased to 10.63/pit after the BII operation,while it diminished to 5.23/pit after RY diversion, this beingthe same level as with the RY procedure alone. AH maintaineda high rate of BrdU incorporation at 12.7% after BII operation,which was also significantly reduced (P < 0.01) to 7.0% bythe RY surgery. The intestinal type cell showed highest (22.2%),the surface mucous type cell showed the next (16.5%) and thepyloric gland type cell showed lowest (5.2%) BrdU labeling indicesafter BII operation. All the cell types in AH showed similarproportional decreases in BrdU incorporation after RY diversion.Thus surgical intervention reverses the cell proliferation causedby bile reflux in the gastric stump. 相似文献
16.
Akitaka Yamasaki Kumiko Maruyama-Takahashi Kento Nishida Shogo Okazaki Kouki Okita Yasutoshi Akiyama Hideaki Suzuki Yuichi Endo Kazue Masuko Takashi Masuko Yoshihisa Tomioka 《Genes to cells : devoted to molecular & cellular mechanisms》2023,28(5):374-382
Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa. 相似文献
17.
Omoto M Imai T Seki K Nomura R Otahara Y 《Environmental health and preventive medicine》1997,2(3):105-116
Based on the fact that chemical products such as binding agents are produced by mixing three kinds of phosphates with different
ratios, we mixed metaphosphate, polyphosphate and pyrophosphate. Each was made to Na-phosphate, K-phosphate, and Ca-phosphate
and each was mixed with commercial feeds so that the content of P would be approximately 0.1, 0.15, 0.3, 0.4, 0.6 and 1.0%.
The prepared pellets were given to ICR, CF # 1 and AKR strains of mice at 29 days of age for 680 days and observations were
made through this experimental period at different stages. The observations were also carried out on the mice administered
with the experimental feeds for 1.5 months from 9 to 10.5 months of age. The observations were compared with those of the
control group at all times. As a result, plasma 1 α, 25 (OH)2 D3 and P levels were always significantly higher in the phosphate administered groups relative to the control. Urine P and Fe
increased while urine Ca decreased in the phosphate-treated groups.
The effect of phosphates on the bones was studied taking soft X-ray pictures of hind legs and applying microdensitometry to
them. Through these observations we recognized thinning of the cortex of bones, reduction of marrow trabecules and development
of osteophyte. Histological observations disclosed that changes in knee joint tissues were apparent; that is, a decrease in
or an irregular loss of the number of cells in superficial, intermediate, and radial strata of the joint cartilage, proliferation
of subchondral bone, and the development of osteophytes were noted. As for muscles, diameters of musclar fibers became smaller;
in particular, type II fibers showed greater shrinkage. Regarding kidneys, swelling and atrophy of glomerular capillaries,
proliferation of mesangial cells, nephroselerosis, swelling, thinning, and loss of tubular epithelium, interstitial tissue
inflammation, development of cylindruria, and deposition of calcium were observed. All these changes seem to be a particularly
advanced aspect of the changes which are more pronounced with increasing dose and age.
These changes were found even in the group administered with the feed containing 0.1% phosphorus, and, these changes were
dependent on the concentration level of P. It was observed that administration to older subjects for a short term (1.5 months)
produced effects stronger than those to younger subjects administered for a long term (10.5 months).
The effects of condensed Ca-phosphate on bones were similar to those of condensed Na- and K-phosphates, and, hence, it was
supposed that these effects were caused by phosphate radicals.
An erratum to this article is available at . 相似文献
18.
Osamu Mikami Shigenari Kawakita Kumiko Fujise Koh Shingu Hakuo Takahashi Tadashi Matsuda 《The Journal of urology》1996,155(4):1368-1371
Purpose
We evaluated plasma catecholamine levels during pneumoperitoneum in laparoscopic surgery.Materials and Methods
Plasma epinephrine and norepinephrine were evaluated in 29 patients who underwent laparoscopic retroperitoneal surgery in a half lateral decubitus position (group 1) or laparoscopic varicocelectomy in a Trendelenburg position (group 2).Results
The levels of epinephrine and norepinephrine increased significantly 5 minutes after carbon dioxide insufflation compared to levels after Veress needle insertion and just before insufflation. The elevation of catecholamine levels during laparoscopic procedures was greater in group 1.Conclusions
Our results indicate that carbon dioxide insufflation may cause catecholamine release during laparoscopic surgery. Careful monitoring of hemodynamics is mandatory at the beginning of the procedure. 相似文献19.
20.
Tomoko Akahane Kenta Masuda Akira Hirasawa Yusuke Kobayashi Arisa Ueki Miho Kawaida Kumiko Misu Kohei Nakamura Shimpei Nagai Tatsuyuki Chiyoda Wataru Yamagami Shigenori Hayashi Fumio Kataoka Kouji Banno Kokichi Sugano Hajime Okita Kenjiro Kosaki Hiroshi Nishihara Daisuke Aoki 《Journal Of Gynecologic Oncology》2022,33(4)
ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control. 相似文献