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Search Results: 1 - 10 of 1163 matches for " Osamu Tokunaga "
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Hematological- and Neurological-Expressed Sequence 1 Gene Products in Progenitor Cells during Newt Retinal Development
Tatsushi Goto,Fumio Tokunaga,Osamu Hisatomi
Stem Cells International , 2012, DOI: 10.1155/2012/436042
Abstract: Urodele amphibians such as Japanese common newts have a remarkable ability to regenerate their injured neural retina, even as adults. We found that hematological- and neurological-expressed sequence 1 (Hn1) gene was induced in depigmented retinal pigment epithelial (RPE) cells, and its expression was maintained at later stages of newt retinal regeneration. In this study, we investigated the distribution of the HN1 protein, the product of the Hn1 gene, in the developing retinas. Our immunohistochemical analyses suggested that the HN1 protein was highly expressed in an immature retina, and the subcellular localization changed during this retinogenesis as observed in newt retinal regeneration. We also found that the expression of Hn1 gene was not induced in mouse after retinal removal. Our results showed that Hn1 gene can be useful for detection of undifferentiated and dedifferentiated cells during both newt retinal development and regeneration. 1. Introduction The vertebrate retina is a tissue specialized in receiving photons and in generating electrical signals which are sent to the brain. The neural retina is a highly organized neural tissue, which is unable to be regenerated in mammals. In contrast, Urodele amphibians such as Japanese common newts (Cynops pyrrhogaster) have an amazing ability to regenerate their retina, even as adults [1, 2]. Studies on this process of retinal regeneration may help to understand the mechanism of neural retina formation and to rescue patients from blindness. The regeneration process of newt retinas has been investigated morphologically for many years [3, 4]. When the neural retinas are surgically removed from newt eyes, the regeneration takes place in the following order [5, 6]. First, the remaining retinal pigment epithelial (RPE) cells lose their pigment granules (depigmentation) and transdifferentiate into retinal progenitor cells [7–9]. Subsequently, these retinal progenitor cells proliferate and differentiate into various neurons and glial cells to reconstruct a neural retina [10]. The retinal regeneration processes usually complete within 5-6 weeks, and newts recover their vision at about 3 months when the optic nerve connects to visual centers in the brain [11]. Although it has been suggested that most processes of retinal regeneration are similar to that of retinal development [10, 12–15], the dedifferentiation of RPE cells is a unique and important event for regeneration. We carried out differential display analyses and found that the hematological, and neurological-expressed sequence 1 (Hn1) gene was
Tuberous Sclerosis Complex Associated with Papillary Serous Carcinoma of the Peritoneum, Lymphangioleiomyomatosis, and Angiomyolipoma
Tomihiro Wakamiya,Yasuo Sugita,Mariko Hashiguchi,Tsuyoshi Iwasaka,Osamu Tokunaga
Case Reports in Pathology , 2011, DOI: 10.1155/2011/564260
Abstract: Tuberous sclerosis complex (TSC) is associated with benign and malignant tumors, including lymphangioleiomyomatosis (LAM) and angiomyolipoma (AML). We herein describe the TSC case of a 50-year-old woman having a papillary serous carcinoma of the peritoneum (PSCP), LAM, and AML. On microscopic examination, the PSCP cells showed a cuboidal to columnar shape, proliferated into the papillae, and infiltrated into the peritoneal cavity and anterior thoracic wall. On immunohistochemical evaluation, the tumor cells were positive for epithelial membrane antigen, human epidermal cytokeratins, and progesterone receptor, but negative for calretinin, carcinoembryonic antigen, MCF-7 cell line (Ber-EP4), and estrogen receptor.
Structural and Functional Analyses of DNA-Sensing and Immune Activation by Human cGAS
Kazuki Kato, Ryohei Ishii, Eiji Goto, Ryuichiro Ishitani, Fuminori Tokunaga, Osamu Nureki
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076983
Abstract: The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.
Analysis of Extrahepatic Multiple Primary Malignancies in Patients with Hepatocellular Carcinoma according to Viral Infection Status
Keita Kai,Atsushi Miyoshi,Kenji Kitahara,Masanori Masuda,Yukari Takase,Kohji Miyazaki,Hirokazu Noshiro,Osamu Tokunaga
International Journal of Hepatology , 2012, DOI: 10.1155/2012/495950
Abstract: Previous studies have investigated extrahepatic multiple primary malignancy (EHPM) associated with hepatocellular carcinoma (HCC). However, its correlation with viral infection, such as hepatitis B virus (HBV) or hepatitis C virus (HCV), has not been examined. The aim of this study is to investigate the association between EHPM and hepatitis infection in HCC patients. A total of 412 patients who underwent surgical resection for primary HCC were enrolled. Viral infection was evaluated by serum HBV surface antigen (HBs Ag) and HCV antibody (HCV Ab). Sixty-eight (16.5%) patients had one or more EHPM. The most frequent EHPM was gastric cancer ( ) in this cohort. No statistical significance was observed in the distribution of viral infection and incidence of entire EHPM. However, HCV Ab, HBs Ag, and negative status for both were correlated with the frequency of gastric ( ), urinary tract ( ), and breast cancer ( ), respectively. Infection of Helicobacter pylori was investigated by immunohistochemistry in gastric EHPM and resulted that 20 out of 21 analyzed cases were negative for Helicobacter pylori. Although it should be verified by well-designed large cohort studies, the current results suggested correlation between HCV infection and gastric cancer, HBV infection and urinary tract cancer and viral hepatitis-free status and breast cancer in HCC patients. 1. Introduction Extrahepatic multiple primary malignancy (EHPM) associated with hepatocellular carcinoma (HCC) has been investigated in previous reports [1–15]. However, the majority of these studies were performed decades ago. The improved survival rates in HCC patients, advances in diagnostic modalities and clinical treatments, and long-term followup might produce a higher incidence of EHPM as well as useful information for the treatment of HCC patients. Although chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are well-known risk factors and are the most influential determinants for HCC, there have been few investigations of the correlation between viral infection status and EHPM. The aim of this study is to reveal the characteristics of EHPM in a cohort receiving long-term followup as well as the association between EHPM and the viral infection status in HCC patients. 2. Materials and Methods 2.1. Patients A total of 412 patients, who underwent a surgical resection for primary HCC between 1984 and December 2010 at Saga University Hospital, were included in this study. Informed consent for the use of medical information was obtained from all patients and the study protocol
SPF-CellTracker: Tracking multiple cells with strongly-correlated moves using a spatial particle filter
Osamu Hirose,Shotaro Kawaguchi,Terumasa Tokunaga,Yu Toyoshima,Takayuki Teramoto,Sayuri Kuge,Takeshi Ishihara,Yuichi Iino,Ryo Yoshida
Computer Science , 2015,
Abstract: Tracking many cells in time-lapse 3D image sequences is an important challenging task of bioimage informatics. Motivated by a study of brain-wide 4D imaging of neural activity in C. elegans, we present a new method of multi-cell tracking. Data types to which the method is applicable are characterized as follows: (i) cells are imaged as globular-like objects, (ii) it is difficult to distinguish cells based only on shape and size, (iii) the number of imaged cells ranges in several hundreds, (iv) moves of nearly-located cells are strongly correlated and (v) cells do not divide. We developed a tracking software suite which we call SPF-CellTracker. Incorporating dependency on cells' moves into prediction model is the key to reduce the tracking errors: cell-switching and coalescence of tracked positions. We model target cells' correlated moves as a Markov random field and we also derive a fast computation algorithm, which we call spatial particle filter. With the live-imaging data of nuclei of C. elegans neurons in which approximately 120 nuclei of neurons are imaged, we demonstrate an advantage of the proposed method over the standard particle filter and a method developed by Tokunaga et al. (2014).
Calcium Participates in Secretion of Porphyrin from Shell Gland Epithelial Cells of Japanese Quail (Coturnix coturnix japonica)  [PDF]
Osamu Kai
Open Journal of Animal Sciences (OJAS) , 2019, DOI: 10.4236/ojas.2019.91013

To investigate factors involved in the secretion of protoporphyrin IX (PpIX), a superficial eggshell pigment, from shell gland epithelial cells of Japanese quail, we cultured cells in Ham’s F12 medium with calcium chloride and quail plasma. The addition of hormones (prostaglandin F2α, progesterone, estradiol-17β) to the medium did not change the PpIX concentration in the culture supernatant, but changing the calcium chloride (CaCl2) concentration did: a lower concentration of CaCl2 led to a higher PpIX concentration; 0 mM CaCl2 enhanced the secretion of PpIX from epithelial cells prepared at 5 or 7 mM CaCl2. The result suggests that a drop in concentration of CaCl2 mimics the end of shell calcification and stimulates rapid secretion of PpIX in vivo. Bovine serum albumin was almost as effective

Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors
Tsuyoshi Mitsuishi, Yukie Iwabu, Kenzo Tokunaga, Tetsutaro Sata, Takehiko Kaneko, Kuniaki Ohara, Ikuroh Ohsawa, Fumino Oda, Yuko Yamada, Seiji Kawana, Kohji Ozaki, Mayuka Nakatake, Osamu Yamada
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-118
Abstract: We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity.Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression.Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.Telomerase is a ribonucleoprotein reverse transcriptase (RT) complex that adds telomeric TTAGGG repeat sequences to chromosomes by using an intrinsic RNA component as template [1,2]. Human telomerase consists of RNA components and a catalytic subunit of human telomerase RT (hTERT), and is coimmunoprecipitated with Akt kinase, heat shock protein 90, the mammalian target of rapamycin (mTOR), and p70 ribosomal protein S6 kinase 1 (S6K1) [3]. Transcription factors c-Myc, SP1, estrogen receptor, E2F-1, WT-1, NFκB and MZF-2 are involved in regulation of hTERT gene expression [4
A Small-Animal Pharmacokinetic/Pharmacodynamic PET Study of Central Serotonin 1A Receptor Occupancy by a Potential Therapeutic Agent for Overactive Bladder
Yosuke Nakatani, Michiyuki Suzuki, Masaki Tokunaga, Jun Maeda, Miyuki Sakai, Hiroki Ishihara, Takashi Yoshinaga, Osamu Takenaka, Ming-Rong Zhang, Tetsuya Suhara, Makoto Higuchi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075040
Abstract: Serotonin 1A (5-HT1A) receptors have been mechanistically implicated in micturition control, and there has been a need for an appropriate biomarker surrogating the potency of a provisional drug acting on this receptor system for developing a new therapeutic approach to overactive bladder (OAB). Here, we analyzed the occupancy of 5-HT1A receptors in living Sprague-Dawley rat brains by a novel candidate drug for OAB, E2110, using positron emission tomography (PET) imaging, and assessed the utility of a receptor occupancy (RO) assay to establish a pharmacodynamic index translatable between animals and humans. The plasma concentrations inducing 50% RO (EC50) estimated by both direct and effect compartment models were in good agreement. Dose-dependent therapeutic effects of E2110 on dysregulated micturition in different rat models of pollakiuria were also consistently explained by achievement of 5-HT1A RO by E2110 in a certain range (≥ 60%). Plasma drug concentrations inducing this RO range and EC50 would accordingly be objective indices in comparing pharmacokinetics-RO relationships between rats and humans. These findings support the utility of PET RO and plasma pharmacokinetic assays with the aid of adequate mathematical models in determining the in vivo characteristics of a drug acting on 5-HT1A receptors and thereby counteracting OAB.
Metal Dependence of Signal Transmission through MolecularQuantum-Dot Cellular Automata (QCA): A Theoretical Studyon Fe, Ru, and Os Mixed-Valence Complexes
Ken Tokunaga
Materials , 2010, DOI: 10.3390/ma3084277
Abstract: Dynamic behavior of signal transmission through metal complexes [L5M-BL-ML5]5+ (M=Fe, Ru, Os, BL=pyrazine ( py), 4,4’-bipyridine ( bpy), L=NH3), which are simplified models of the molecular quantum-dot cellular automata (molecular QCA), is discussed from the viewpoint of one-electron theory, density functional theory. It is found that for py complexes, the signal transmission time (tst) is Fe(0.6 fs) < Os(0.7 fs) < Ru(1.1 fs) and the signal amplitude (A) is Fe(0.05 e) < Os(0.06 e) < Ru(0.10 e). For bpy complexes, tst and A are Fe(1.4 fs) < Os(1.7 fs) < Ru(2.5 fs) and Os(0.11 e) < Ru(0.12 e)
Satoko Tokunaga
International Journal of English Studies (IJES) , 2005, DOI: 10.6018/ijes.5.2.47761
Abstract: This paper examines soine distinctive uses of typefaces by Caxton's compositors in his early products at Westminster and illustrates how useful such examples are in revealing the chronology of actual book production, as well as in identifying the compositors at work on individual volumes. An exhaustive analysis of early printed books can provide us with information about compositors at work in England's earliest printing house. This paper therefore argues that it is inost definitely worth considering such 'inechaiiical' aspects of book design as typography when editing any printed text, and introduces most recent research results contributed by a project at Keio University, which airns to establish a semiautomatic system that can transcribe every feature of the printed text including even minute differences in types.
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