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91.
Erika Ishihara Yuya Nagaoka Toshiaki Okuno Satoshi Kofuji Mari Ishigami‐Yuasa Hiroyuki Kagechika Kenya Kamimura Shuji Terai Takehiko Yokomizo Yukihiko Sugimoto Yasuyuki Fujita Akira Suzuki Hiroshi Nishina 《Genes to cells : devoted to molecular & cellular mechanisms》2020,25(3):197-214
Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by “normal” MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE2 secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition. 相似文献
92.
Junya Ohtake Takayuki Ohkuri Yuji Togashi Hidemitsu Kitamura Kiyotaka Okuno Takashi Nishimura 《Immunology letters》2014
We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01. The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02. This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4+ and CD8+ T cells though it contained both helper and killer epitopes. To enhance the vaccine efficacy, we synthesized a long peptide by conjugating SU18 peptide and another DR53-restricted helper epitope peptide (SU22; 12 amino-acids) using glycine-linker. We designated this artificial 40 amino-acids long peptide containing two helper and three killer epitopes as Survivin-helper/killer-hybrid epitope long peptide (Survivin-H/K-HELP). Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4+ Th1 cells and CD8+ Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC). Survivin-H/K-HELP-pulsed Mo-DC pretreated with OK-432 also exhibited sustained antigen-presentation capability of stimulating Survivin-specific Th1 cells compared with Mo-DC pulsed with a mixture of SU18 and SU22 short peptides. Moreover, we demonstrated that Survivin-H/K-HELP induced a complete response in a breast cancer patient with the induction of cellular and humoral immune responses. Thus, we believe that an artificially synthesized Survivin-H/K-HELP will become an innovative cancer vaccine. 相似文献
93.
Biotin and carnitine deficiency due to hypoallergenic formula nutrition in infants with milk allergy
Hisako Hayashi Shuko Tokuriki Takashi Okuno Yosuke Shigematsu Akiba Yasushi Go Matsuyama Ken Sawada Yusei Ohshima 《Pediatrics international》2014,56(2):286-288
Amino acid formulas and hydrolyzed formulas given to infants in Japan with milk allergies theoretically contain little, if any, biotin and carnitine. We assessed biotin and carnitine insufficiency in six infants with milk allergy who were fed amino acid formulas and/or hydrolyzed formulas, by measuring urine 3‐hydroxyisovaleric acid (3‐HIA) and serum free carnitine (C0), respectively. All patients presented with elevated urine 3‐HIA and lowered serum C0 compared with post‐menstrual age‐matched infants who were fed breast milk or standard infant formulas. Supplementation with biotin and l ‐carnitine immediately improved the insufficiency. Care should be taken to avoid biotin and carnitine deficiency in allergic infants fed amino acid or hydrolyzed formulas. 相似文献
94.
Shinji Tokuyama Hidekazu Takahashi Norikatsu Miyoshi Naotsugu Haraguchi Taishi Hata Chu Matsuda Hirofumi Yamamoto Tsunekazu Mizushima Masaki Mori Yuichiro Doki 《Asian journal of endoscopic surgery》2020,13(2):227-230
A 31‐year‐old man with pain in his thigh was diagnosed with a benign presacral cystic mass. We performed laparoscopic subtotal resection of the cyst utilizing mobilization of a total mesorectal excision procedure used in low anterior resection for rectal cancer. Histopathological findings showed that the cystic lumen of the specimen was lined with pseudostratified columnar ciliated epithelium and had glandular structures and smooth muscle in its wall, leading to a diagnosis of bronchogenic cyst. The postoperative course was uneventful, and as of 6 months after surgery, the patient was doing well with no evidence of recurrence. 相似文献
95.
Ayako Sakakibara Kei Kohno Eri Ishikawa Yuka Suzuki Yuta Tsuyuki Satoko Shimada Kazuyuki Shimada Akira Satou Taishi Takahara Akiko Ohashi Emiko Takahashi Seiichi Kato Shigeo Nakamura Naoko Asano 《Journal of Clinical and Experimental Hematopathology》2021,61(4):182
The programmed cell death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumor cell escape from immune control and has been most extensively investigated for therapeutic purposes. However, PD-L1 immunohistochemistry is still not used widely for diagnosis. We review the diagnostic utility of PD-L1 (by clone SP142) immunohistochemistry in large-cell lymphomas, mainly consisting of classic Hodgkin lymphoma (CHL) and diffuse large B-cell lymphoma (DLBCL). Neoplastic PD-L1 (nPD-L1) expression on Hodgkin and Reed-Sternberg cells is well-established among prototypic CHL. Of note, EBV+ CHL often poses a challenge for differential diagnosis from peripheral T-cell lymphoma with EBV+ non-malignant large B-cells; their distinction is based on the lack of PD-L1 expression on large B-cells in the latter. The nPD-L1 expression further provides a good diagnostic consensus for CHL with primary extranodal disease conceivably characterized by a combined pathogenesis of immune escape of tumor cells and immunodeficiency. Compared with CHL, the nPD-L1 expression rate is much lower in DLBCL, highlighting some specific subgroups of intravascular large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and EBV+ DLBCL. They consist of nPD-L1-positive and -negative subgroups, but their clinicopathological significance remains to be elucidated. Microenvironmental PD-L1 positivity on immune cells may be associated with a favorable prognosis in extranodal DLBCL. PD-L1 (by SP142) immunohistochemistry has helped us to understand the immune biology of lymphoid neoplasms possibly related by immune escape and/or immunodeficiency. However, knowledge of these issues remains limited and should be clarified for diagnostic consensus in the future. 相似文献
96.
97.
98.
Kazuyuki Furuta Mayuko Natsuhara Hirotsugu Takano Soken Tsuchiya Yasushi Okuno Hiroshi Ohtsu Masahiro Nishibori Robin L. Thurmond Noriyasu Hirasawa Kazuhisa Nakayama Atsushi Ichikawa Yukihiko Sugimoto Satoshi Tanaka 《European journal of immunology》2014,44(1):204-214
Mast cells are the major sources of histamine, which is released in response to immunological stimulations. The synthesis of histamine is catalyzed by histidine decarboxylase (HDC). Previous studies have shown that Hdc?/? mast cells exhibit aberrant granule morphology with severely decreased granule content. Here, we investigated whether the histamine synthesized in mast cells regulates the granule maturation of murine mast cells. Several genes, including those encoding granule proteases and enzymes involved in heparin biosynthesis, were downregulated in Hdc?/? peritoneal mast cells. Impaired granule maturation was also found in Hdc?/? BM‐derived cultured mast cells when they were cocultured with fibroblasts in the presence of c‐kit ligand. Exogenous application of histamine and several H4 receptor agonists restored the granule maturation of Hdc?/? cultured mast cells. However, the maturation of granules was largely normal in Hrh4?/? peritoneal mast cells. Depletion of cellular histamine with tetrabenazine, an inhibitor of vesicular monoamine transporter‐2, did not affect granule maturation. In vivo experiments with mast cell deficient KitW/KitW‐v mice indicated that the expression of the Hdc gene in mast cells is required for granule maturation. These results suggest that histamine promotes granule maturation in mast cells and acts as an proinflammatory mediator. 相似文献
99.
Toshiomi Okuno Koichi Yamanishi Kimiyasu Shiraki Junko Namazue Michiaki Takahashi 《Virus research》1988,10(4):357-367
HL-60 cells can be induced to differentiate into macrophage-like cells by treatment with 12-O-tetra-decanoylphorbol-13-acetate (TPA). The relationship between virus replication and cell differentiation was investigated using HL-60 cells that had been induced to differentiate by TPA (dHL-60 cells) and undifferentiated cells (udHL-60 cells). On infection of these cells with cell-free varicella-zoster virus (VZV), virus antigens were detected in dHL-60 cells but not in udHL-60 cells, and the percentage of antigen-positive dHL-60 cells increased during incubation. Similar results were obtained by infectious center assay, and the percentage of antigen-positive cells correlated with the stage of cell differentiation. No significant difference was found in the binding of VZV to dHL-60 cells and udHL-60 cells. Furthermore, trypsin treatment after adsorption suggested that VZV penetrated into udHL-60 cells. These findings indicate that VZV may be able to replicate in mature monocytes but may be harbored in immature monocytes in vivo. 相似文献
100.