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91.
Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice 总被引:19,自引:0,他引:19
Okazaki T Tanaka Y Nishio R Mitsuiye T Mizoguchi A Wang J Ishida M Hiai H Matsumori A Minato N Honjo T 《Nature medicine》2003,9(12):1477-1483
We recently reported that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against a heart-specific, 30-kDa protein. In this study, we purified the 30-kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal antibodies to cTnI induced dilatation and dysfunction of hearts in wild-type mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and augmented the voltage-dependent L-type Ca2+ current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes. 相似文献
92.
Ariizumi T Kinoshita M Yokota C Takano K Fukuda K Moriyama N Malacinski GM Asashima M 《The International journal of developmental biology》2003,47(6):405-410
Amphibian embryos are an excellent model system for analyzing the mechanisms of vertebrate cardiogenesis. Studies of heart development in Xenopus have, for example, revealed that the inductive interaction of the heart primordia with the adjacent underlying endoderm and dorsal lip starts at the early stages of gastrulation. However, the molecular basis of those early inductive events and the genes expressed during the early phases of heart differentiation remain largely unknown. Amphibian blastula embryos contain pluripotent cells in their ectodermal region, called the "animal cap," which fortunately can be exploited for understanding a variety of organogenesis processes. Despite an enormous potential for analysis, the use of this system in cardiogenesis research has languished due to a lack of information concerning appropriate culture methods. Herein we report conditions for generating an in vitro heart induction system and present evidence from two types of in vivo transplantations, that the cultured heart rudiment can develop and function in the adult organism. It is expected that the fundamental principles established in this model system will provide a versatile research platform for a variety of organ engineering projects, including modifying in vitro organ growth with exogenous components (e.g. various growth factors) and developing methods for preparing tissue for transplantation. 相似文献
93.
94.
Naoki Utsunomiya Suranant Subhadrabandhu Keizo Yonemori Masayoshi Oshida Shinya Kanzaki Fumiaki Nakatsubo Akira Sugiura 《Economic botany》1998,52(4):343-351
Diospyros species distributed widely in Thailand were classified into four ecotypes, according to their habitat; constantly humid area,
alternately dry and wet area, mountainous cool area and all area. Some of them inhabit near dwelling areas or in the paddy
field in the village. The young fruit is covered with dense pubescence in most species. The size, shape, and color of mature
fruit greatly vary greatly with the species. In most species, the mature fruit has a soft pulp and hard skin. The fruit of
six species has been used for dying. Four species produce edible fruits, with color and flavor favorable for breeding of edibleDiospyros species. The fruit of some species contains some chemicals useful as fish poisoning or of medicines, although the active
components have not yet been identified. The edible fruit contained many tannin cells, but the fruit used as fish poisoning
and medicines had only a few. 相似文献
95.
96.
97.
Masayoshi Shinjoh Norio Sugaya Yoshio Yamaguchi Yuka Tomidokoro Shinichiro Sekiguchi Keiko Mitamura Motoko Fujino Hiroyuki Shiro Osamu Komiyama Nobuhiko Taguchi Yuji Nakata Naoko Yoshida Atsushi Narabayashi Michiko Myokai Masanori Sato Munehiro Furuichi Hiroaki Baba Hisayo Fujita Akihiro Sato Ichiro Ookawara Kenichiro Tsunematsu Makoto Yoshida Mio Kono Fumie Tanaka Chiharu Kawakami Takahisa Kimiya Takao Takahashi Satoshi Iwata Keio Pediatric Influenza Research Group 《PloS one》2015,10(8)
We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013–14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B. 相似文献
98.
Nobukatsu Horita Kiichiro Tsuchiya Ryohei Hayashi Keita Fukushima Shuji Hibiya Masayoshi Fukuda Yoshihito Kano Tomohiro Mizutani Yasuhiro Nemoto Shiro Yui Ryuichi Okamoto Tetsuya Nakamura Mamoru Watanabe 《Biochemical and biophysical research communications》2014
Background and aims
The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour.Methods
Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence.Results
We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids.Conclusions
The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus. 相似文献99.
Masashi Iwamoto Koichi Watashi Senko Tsukuda Hussein Hassan Aly Masayoshi Fukasawa Akira Fujimoto Ryosuke Suzuki Hideki Aizaki Takayoshi Ito Osamu Koiwai Hiroyuki Kusuhara Takaji Wakita 《Biochemical and biophysical research communications》2014
Hepatitis B virus (HBV) entry has been analyzed using infection-susceptible cells, including primary human hepatocytes, primary tupaia hepatocytes, and HepaRG cells. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) membrane transporter was reported as an HBV entry receptor. In this study, we established a strain of HepG2 cells engineered to overexpress the human NTCP gene (HepG2-hNTCP-C4 cells). HepG2-hNTCP-C4 cells were shown to be susceptible to infection by blood–borne and cell culture-derived HBV. HBV infection was facilitated by pretreating cells with 3% dimethyl sulfoxide permitting nearly 50% of the cells to be infected with HBV. Knockdown analysis suggested that HBV infection of HepG2-hNTCP-C4 cells was mediated by NTCP. HBV infection was blocked by an anti-HBV surface protein neutralizing antibody, by compounds known to inhibit NTCP transporter activity, and by cyclosporin A and its derivatives. The infection assay suggested that cyclosporin B was a more potent inhibitor of HBV entry than was cyclosporin A. Further chemical screening identified oxysterols, oxidized derivatives of cholesterol, as inhibitors of HBV infection. Thus, the HepG2-hNTCP-C4 cell line established in this study is a useful tool for the identification of inhibitors of HBV infection as well as for the analysis of the molecular mechanisms of HBV infection. 相似文献
100.
Mariko Kato Nahoko Nagasaki-Takeuchi Yuki Ide Rie Tomioka Masayoshi Maeshima 《Plant signaling & behavior》2010,5(7):848-850
In plants, Ca2+, phosphatidylinositol phosphates (PtdInsPs) and inositol phosphates are major components of intracellular signaling. Several kinds of proteins and enzymes, such as calmodulin (CaM), protein kinase, protein phosphatase, and the Ca2+ channel, mediate the signaling. Two new Ca2+-binding proteins were identified from Arabidopsis thaliana and named PCaP1 and PCaP2 [plasma membrane (PM)-associated Ca2+(cation)-binding protein 1 and 2]. PCaP1 has an intrinsically disordered region in the central and C-terminal parts. The PCaP1 gene is expressed in most tissues and the PCaP2 gene is expressed predominantly in root hairs and pollen tubes. We recently demonstrated that these proteins are N-myristoylated, stably anchored in the PM, and are bound with phosphatidylinositol phosphates, especially PtdInsP2s. Here we propose a model for the switching mechanism of Ca2+-signaling mediated by PtdInsPs. Ca2+ forms a complex with CaM (Ca2+-CaM) when there is an increase in the cytosol free Ca2+. The binding of PCaPs with Ca2+-CaM causes PCaPs to release PtdInsPs. Until the release of PtdInsPs, the signaling is kept in the resting state.Key words: calcium signal, calmodulin, inositol phosphate, intrinsically disordered protein, myristoylation, phosphatidylinositol phosphate, plasma membrane 相似文献