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Tadashi Yamashita 대한당뇨병학회 2011 Diabetes and Metabolism Journal Vol.35 No.4
Glycosphingolipids (GSLs) are present in all mammalian cell plasma membranes and intracellular membrane structures. They are especially concentrated in plasma membrane lipid domains that are specialized for cell signaling. Plasma membranes have typical structures called rafts and caveola domain structures, with large amounts of sphingolipids, cholesterol, and sphingomyelin. GSLs are usually observed in many organs ubiquitously. However, GSLs, including over 400 derivatives, participate in diverse cellular functions. Several studies indicate that GSLs might have an effect on signal transduction related to insulin receptors and epidermal growth factor receptors. GSLs may modulate immune responses by transmitting signals from the exterior to the interior of the cell. Guillain-Barré syndrome is one of the autoimmune disorders characterized by symmetrical weakness in the muscles of the legs. The targets of the immune response are thought to be gangliosides, which are one group of GSLs. Other GSLs may serve as second messengers in several signaling pathways that are important to cell survival or programmed cell death. In the search for clear evidence that GSLs may play critical roles in various biological functions, many researchers have made genetically engineered mice. Before the era of gene manipulation, spontaneous animal models or chemical-induced disease models were used.
Shintaro Honda,Satoshi Ota,Shinnosuke Yamashita,Tadashi Yasuda 대한골다공증학회 2022 Osteoporosis and Sarcopenia Vol.8 No.1
Objectives: Fragility fractures of the pelvis (FFP) commonly occur in the frail elderly. Displacement in the posterior pelvic ring is recognized as the key sign of instability. This study aims to elucidate the relationship between computer tomography (CT)-based frailty markers and displacement of the posterior pelvic ring within 7 days after injury. Methods: This retrospective study included 49 patients (42 females, 7 males) with FFP (type I 10, type II 24, type III 12, type IV 3). On a CT slice at the level of the third lumbar vertebra, skeletal muscle area, skeletal muscle radiation attenuation, and skeletal muscle index (SMI) were calculated as sarcopenia markers. Osteopenia was measured with trabecular region of interest attenuation technique on the same CT slice. Results: There was no difference in the demographics between non-displaced and displaced FFP. CT-based data showed that patients with FFP had osteopenia. However, no difference was found between non-displaced and displaced FFP. SMI was higher in FFP types III/IV than non-displaced FFP when CT-based data on sarcopenia were compared among all patients. Female patients with FFP demonstrated similar results. Logistic regression analysis using the demographics and CT-based markers on sarcopenia and osteopenia revealed that SMI was a potential determinant of displacement of the posterior pelvic ring fractures. Conclusions: There was inverse association between sarcopenia and displacement of the posterior pelvic ring in the early phase of FFP. Relatively preserved muscle may develop displacement in the elderly with osteopenia.
( Tae Bon Koo ),( Min Su Han ),( Yamashita Tadashi ),( Won Joon Seong ),( Je Yong Choi ) 생화학분자생물학회(구 한국생화학분자생물학회) 2013 BMB Reports Vol.46 No.10
Invasion of trophoblasts into maternal uterine tissue is essential for establishing mature feto-maternal circulation. The trophoblast invasion associated with placentation is similar to tumor invasion. In this study, we investigated the role of KAI1, an anti-metastasis factor, at the maternal-fetal interface during placentation. Mouse embryos were obtained from gestational days 5.5 (E5.5) to E13.5. Immunohistochemical analysis revealed that KAI1 was expressed on decidual cells around the track made when a fertilized ovum invaded the endometrium, at days E5.5 and E7.5, and on trophoblast giant cells, along the central maternal artery of the placenta at E9.5. KAI1 in trophoblast giant cells was increased at E11.5, and then decreased at E13.5. Furthermore, KAI1 was upregulated during the forskolinmediated trophoblastic differentiation of BeWo cells. Collectively, these results indicate that KAI1 is differentially expressed in decidual cells and trophoblasts at the maternal-fetal interface, suggesting that KAI1 prevents trophoblast invasion during placentation. [BMB Reports 2013; 46(10): 507-512]
Yoon, Jeong-Hwan,Jung, Su Myung,Park, Seok Hee,Kato, Mitsuyasu,Yamashita, Tadashi,Lee, In-Kyu,Sudo, Katsuko,Nakae, Susumu,Han, Jin Soo,Kim, Ok-Hee,Oh, Byung-Chul,Sumida, Takayuki,Kuroda, Masahiko,Ju, Blackwell Publishing Ltd 2013 EMBO molecular medicine Vol.5 No.11
<P>Varieties of transforming growth factor-β (TGF-β) antagonists have been developed to intervene with excessive TGF-β signalling activity in cancer. Activin receptor-like kinase5 (ALK5) inhibitors antagonize TGF-β signalling by blocking TGF-β receptor-activated Smad (R-Smad) phosphorylation. Here we report the novel mechanisms how ALK5 inhibitors exert a therapeutic effect on a mouse B16 melanoma model. Oral treatment with a novel ALK5 inhibitor, EW-7197 (2.5 mg/kg daily) or a representative ALK5 inhibitor, LY-2157299 (75 mg/kg bid) suppressed the progression of melanoma with enhanced cytotoxic T-lymphocyte (CTL) responses. Notably, ALK5 inhibitors not only blocked R-Smad phosphorylation, but also induced ubiquitin-mediated degradation of the common Smad, Smad4 mainly in CD8<SUP>+</SUP> T cells in melanoma-bearing mice. Accordingly, T-cell-specific deletion of Smad4 was sufficient to suppress the progression of melanoma. We further identified eomesodermin (Eomes), the T-box transcription factor regulating CTL functions, as a specific target repressed by TGF-β via Smad4 and Smad3 in CD8<SUP>+</SUP> T cells. Thus, ALK5 inhibition enhances anti-melanoma CTL responses through ubiquitin-mediated degradation of Smad4 in addition to the direct inhibitory effect on R-Smad phosphorylation.</P>
Sayed Fathi El-Hawari,Norihiko Oyama,Yukako Koyama,Jun Tamura,Takaharu Itami,Tadashi Sano,Kazuto Yamashita 대한수의학회 2022 Journal of Veterinary Science Vol.23 No.4
Background: Problems associated with using inhalational anaesthesia are numerous in veterinary anaesthesia practice. Decreasing the amount of used inhalational anaesthetic agents and minimising of cardiorespiratory disorders are the standard goals of anaesthetists. Objective: This experimental study was carried out to investigate the sparing effect of intravenous tramadol, lidocaine, dexmedetomidine and their combinations on the minimum alveolar concentration (MAC) of sevoflurane in healthy Beagle dogs. Methods: This study was conducted on six beagle dogs. Sevoflurane MAC was determined by the tail clamp method on five separate occasions. The dogs received no treatment (control; CONT), tramadol (TRM: 1.5 mg kg-1 intravenously followed by 1.3 mg kg-1 h-1), lidocaine (LID: 2 mg kg-1 intravenously followed by 3 mg kg-1 h-1), dexmedetomidine (DEX: 2 μg kg-1 intravenously followed by 2 μg kg-1 h-1), and their combination (COMB), respectively. Cardiorespiratory variables were recorded every five minutes and immediately before the application of a noxious stimulus. Results: The COMB treatment had the greatest sevoflurane MAC-sparing effect (67.4 ± 13.9%) compared with the other treatments (5.1 ± 25.3, 12.7 ± 14.3, and 40.3 ± 15.1% for TRM, LID, and DEX treatment, respectively). The cardiopulmonary variables remained within the clinically acceptable range following COMB treatment, although the mean arterial pressure was higher and accompanied by bradycardia. Conclusions: Tramadol-lidocaine-dexmedetomidine co-infusion produced a remarkable sevoflurane MAC-sparing effect in clinically healthy beagle dogs and could result in the alleviation of cardiorespiratory depression caused by sevoflurane. Cardiorespiratory variables should be monitored carefully to avoid undesirable side effects induced by dexmedetomidine.
이현,이종길,배용철,양송현,Nozomu Okino,Edward H. Schuchman,Tadashi Yamashita,배재성,진희경 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.2
In several lysosomal storage disorders, including Niemann-Pick disease Type C (NP-C), sphingolipids, including glycosphingolipids, particularly gangliosides, are the predominant storage materials in the brain, raising the possibility that accumulation of these lipids may be involved in the NP-C neurodegenerative process. However, correlation of these accumulations and NP-C neuropathology has not been fully characterized. Here we derived NP-C mice with complete and partial deletion of the Siat9 (encoding GM3 synthase) gene in order to investigate the role of ganglioside in NP-C pathogenesis. According to our results, NP-C mice with homozygotic deletion of GM3 synthase exhibited an enhanced neuropathological phenotype and died significantly earlier than NP-C mice. Notably, in contrast to complete depletion, NP-C mice with partial deletion of the GM3 synthase gene showed ameliorated NP-C neuropathology, including motor disability, demyelination, and abnormal accumulation of cholesterol and sphingolipids. These findings indicate the crucial role of GM3 synthesis in the NP-C phenotype and progression of CNS pathologic abnormality, suggesting that well-controlled inhibition of GM3 synthesis could be used as a therapeutic strategy.
Lee, Hyun,Lee, Jong Kil,Bae, Yong Chul,Yang, Song Hyun,Okino, Nozomu,Schuchman, Edward H.,Yamashita, Tadashi,Bae, Jae-Sung,Jin, Hee Kyung Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.2
In several lysosomal storage disorders, including Niemann-Pick disease Type C (NP-C), sphingolipids, including glycosphingolipids, particularly gangliosides, are the predominant storage materials in the brain, raising the possibility that accumulation of these lipids may be involved in the NP-C neurodegenerative process. However, correlation of these accumulations and NP-C neuropathology has not been fully characterized. Here we derived NP-C mice with complete and partial deletion of the Siat9 (encoding GM3 synthase) gene in order to investigate the role of ganglioside in NP-C pathogenesis. According to our results, NP-C mice with homozygotic deletion of GM3 synthase exhibited an enhanced neuropathological phenotype and died significantly earlier than NP-C mice. Notably, in contrast to complete depletion, NP-C mice with partial deletion of the GM3 synthase gene showed ameliorated NP-C neuropathology, including motor disability, demyelination, and abnormal accumulation of cholesterol and sphingolipids. These findings indicate the crucial role of GM3 synthesis in the NP-C phenotype and progression of CNS pathologic abnormality, suggesting that well-controlled inhibition of GM3 synthesis could be used as a therapeutic strategy.