33 research outputs found

    New Lymphology Combined with Lymphatic Physiology, Innate Immunology, and Oncology

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    ArticleJournal of Blood & Lymph. 4(2):126 (2014)journal articl

    Pivotal roles of shear stress in the microenvironmental changes that occur within sentinel lymph nodes

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    A sentinel lymph node (SLN) is the first lymph node that receives drainage from a primary tumor. According to their physiological and biomechanical characteristics, we hypothesized that SLN contains lymphatic endothelial cells (LEC) that are constantly loaded with high levels of shear stress, which might contribute to the production of a suitable environment for micrometastasis within them. To test this hypothesis, we investigated the effects of shear stress stimulation on the expression of adhesion molecules on human LEC isolated from the lymph vessels nearest the SLN of breast cancers, and on the release of ATP from human LEC. The study clarified that the shear stress stimulation produced a significant increase of ICAM-1 expression at protein and mRNA levels in human LEC. Next, we examined whether the shear stress-mediated increase of ICAM-1 expression accelerates the attachment of carcinoma cells to human LEC. Finally, in in vivo experiments, we evaluated whether exogenous ATP facilitates the expression of carcinoma cell-ligated adhesion molecules in rat SLN. In conclusion, shear stress stimulation induces ICAM-1 expression on human LEC by activating cell surface F1/FO ATP synthase, which might contribute to the development of a premetastatic environment within SLN. (Cancer Sci 2012; 103: 12451252)ArticleCANCER SCIENCE. 103(7):1245-1252 (2012)journal articl

    Real-time imaging of the lymphatic channels and sentinel lymph nodes of the stomach using contrast-enhanced ultrasonography with Sonazoid in a porcine model

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    The contrast-enhanced ultrasound (CEUS)-guided method in combination with Sonazoid has not been clinically or experimentally evaluated with regard to its use for identifying sentinel lymph node (SLN) in the stomach. Therefore, we attempted to evaluate the usefulness of the CEUS-guided method with Sonazoid for imaging of the lymphatic channels and SLN of the stomach in a porcine model by comparing it with the conventional Evans blue dye-guided method. Twenty-eight 2 to 3-month-old swine weighing 17-30 kg were used in this experiment. Anesthesia was maintained with 2.0-3.0% isoflurane/O(2) inhalation. Sonazoid was injected into the intra-and sub-mucosal layers of the stomach. The intragastric or transcutaneous CEUS-guided method was used to identify the lymphatic channels and SLN of the stomach. Contrast imaging using the CEUS-guided method with Sonazoid enabled us to produce clear images of the afferent lymph vessel and SLN of the stomach until 2 h after the injection of Sonazoid. In addition, intranodal flow of the microbubble agent could be clearly identified using tissue linear harmonic images of the SLN. The SLN detection rate was not significantly different between the CEUS- and dye-guided methods. However, the Evans blue dye flowed out quickly (similar to 15 min after the injection) through the true SLN into the next LN of stomach. In conclusion, the use of the CEUS-guided method with Sonazoid might be the most useful clinical procedure for producing real-time images of the SLN of the stomach, and the linear harmonic images are also useful for evaluating intranodal structure within the SLN. (Cancer Sci 2011; 102: 2073-2081)ArticleCANCER SCIENCE. 102(11):2073-2081 (2011)journal articl

    Thrombin Activates Ca2+-permeating Nonselective Cation Channels through Protein Kinase C in Human Umbilical Vein Endothelial Cells

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    We analyzed Ca-permeating nonselective cation channels (NSCs)mediating thrombin-induced contraction of human umbilical vein endothelial cells (HUVECs). A Ca chelater, BAPTA-AM (10μM), significantly inhibited the thrombin-induced contraction of HUVECs.Thrombin induced inward currents at -60 mV in the presence of intracellular MgATP. Removal of extracellular Caブグsignificantly decreased the currents. A selective phospholipase C inhibitor, U73122 (1μM) but not its inactive analogue, U73343 (1μM) almost completely inhibited the currents. Neither a selective inhibitor of Caブグ-ATPase of endoplasmic reticulum, thapsigargin (1μM)nor a diacylglycerol analogue, 1-oleoyl-2-acetyl-glycerol (30μM)activated the currents. However, a selective protein kinase C inhibitor, bisindolylmaleimide I (500 nM) significantly inhibited the currents.The thrombin-induced currents were significantly inhibited by SKF96365 (50μM)but not by La(1mM), ruthenium red (10μM) or flufenamic acid (100μM). As assessed with RT-PCR, HUVECs expressed transient receptor potential(TRP)M4,7,TRPV1,2,4,TRPC1,4 and 6 subunits of NSCs.These results indicate that thrombin activates Ca-permeating NSCs containing TRPC4 through protein kinase C in HUVECs. Thus,drugs specifically inhibiting TRPC4-containing channels might be effective to control fatal diseases such as sepsis where thrombin mediates the vicious cycle between inflammation and coagulation.Article信州医学雑誌 59(1): 13-26(2011)departmental bulletin pape

    The establishment of new lympholgy: overview

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    ArticleAnnals of Vascular Diseases. 5(3):247-248 (2012)journal articl

    Involvement of ATP-sensitive K +

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