Publications by authors named "Hiroto Yamamoto"

19 Publications

  • Page 1 of 1

TEG6s Platelet Mapping assay for the estimation of plasma fibrinogen concentration during cardiovascular surgery: a single-center prospective observational study.

J Anesth 2021 Oct 13. Epub 2021 Oct 13.

Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Purpose: The Activator F (ActF) test on the TEG6s Platelet Mapping assay system is a means of quantifying blood viscoelasticity caused by fibrin network formation, triggered by reptilase and factor XIII, while platelets are inhibited. This unique methodology enables the measurement of blood viscoelasticity, even in highly heparinized blood. Here, we investigated whether fibrinogen concentration could be estimated using the ActF test in blood samples obtained during cardiopulmonary bypass (CPB) and after CPB in patients undergoing cardiovascular surgery.

Methods: We performed a single-center prospective observational study at a university hospital. Forty patients aged ≥ 18 years who underwent elective cardiovascular surgery with CPB were enrolled. Blood samples were drawn after the induction of anesthesia, after declamping of the aorta during CPB, and after the reversal of heparinization using protamine (after CPB). Coagulation profiles were evaluated using the Platelet Mapping assay and standard laboratory tests.

Results: There were strong correlations between the maximal amplitude of clot strength (MA) in the ActF test and fibrinogen concentration in samples drawn during CPB (R = 0.84, 95% confidence interval [CI] 0.72-0.91; P < 0.001) and after CPB (R = 0.83, 95% CI 0.70-0.91; P < 0.001). The areas under the receiver-operating characteristic curve for the ActF MA for fibrinogen concentrations < 150 mg/dL were 0.86 (95% CI 0.73-1.0) during CPB and 0.98 (95% CI 0.94-1.0) after CPB.

Conclusion: TEG6s Platelet Mapping ActF MA values strongly correlated with plasma fibrinogen concentration in highly heparinized blood during CPB and yielded highly accurate measurements of low fibrinogen concentrations.
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http://dx.doi.org/10.1007/s00540-021-03009-4DOI Listing
October 2021

Acalculous Ischemic Cholecystitis Caused by Spontaneous Celiac Artery Dissection.

Intern Med 2021 Jun 26. Epub 2021 Jun 26.

Department of Diagnostic Pathology, Shimada Municipal Hospital, Japan.

We herein report a case of spontaneous isolated dissection of the celiac artery. A Japanese man in his 50s visited an emergency unit, complaining of sudden epigastralgia. Contrast-enhanced computed tomography indicated dissection of the celiac artery with patent false and true lumina, extending to the splenic and common hepatic arteries. On day 3 of hospitalization, the dissection progressed to the proper and right hepatic arteries. Progression of the dissection to the right hepatic artery provoked acalculous ischemic cholecystitis, and cholecystectomy followed. The resected gallbladder revealed extensive aseptic necrosis with little inflammatory reaction, and the gallbladder neck was spared from ischemia.
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http://dx.doi.org/10.2169/internalmedicine.7793-21DOI Listing
June 2021

Gastric perforation caused by secondary systemic amyloidosis.

Clin Case Rep 2021 May 24;9(5):e04254. Epub 2021 May 24.

Department of Diagnostic Pathology Shimada Municipal Hospital Shimada Japan.

Amyloid A amyloidosis secondary to chronic inflammation involves systemic organs and tissues, including the gastrointestinal tract. In the present case, massive amyloid deposit caused gastric perforation. IgM co-deposition in the glomeruli was another finding of note.
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http://dx.doi.org/10.1002/ccr3.4254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142406PMC
May 2021

Transcriptome analysis of sevoflurane exposure effects at the different brain regions.

PLoS One 2020 15;15(12):e0236771. Epub 2020 Dec 15.

Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Backgrounds: Sevoflurane is a most frequently used volatile anesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis.

Methods: Eight-week old mice were exposed to sevoflurane. RNA from medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted and their gene ontology terms were analysed using Metascape. These our anesthetized mouse data and the transcriptome array data of the cerebral cortex of sleeping mice were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes.

Results: The gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in each region of brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anesthetized mice. Focusing on individual genes, sevoflurane induced Klf4 upregulation in all sampled parts of brain. wPGSA supported the function of KLF4 as a transcription factor, and KLF4-binding motifs were present in many regulatory regions of the differentially expressed genes.

Conclusions: Klf4 was upregulated by sevoflurane inhalation in the mouse brain. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737892PMC
January 2021

Severe COVID-19 Pneumonia in a 30-Year-Old Woman in the 36th Week of Pregnancy Treated with Postpartum Extracorporeal Membrane Oxygenation.

Am J Case Rep 2020 Oct 28;21:e927521. Epub 2020 Oct 28.

Trauma and Acute Critical Care Center, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan.

BACKGROUND There are few reports of coronavirus disease 2019 (COVID-19) in pregnant women. Although coagulation dysfunction was reported to affect the severity of COVID-19, the association between pregnancy, which is usually accompanied by changes in coagulation function, and the worsening of COVID-19 is unknown. We present a case of a 30-year-old woman in the 36th week of pregnancy who was diagnosed with severe COVID-19 pneumonia and required postpartum extracorporeal membrane oxygenation (ECMO) therapy. CASE REPORT A 30-year-old, 36-weeks pregnant woman presented to our hospital and was diagnosed with severe COVID-19 pneumonia soon after she had undergone a cesarean section. Her respiratory failure could not be managed by conventional therapeutic approaches. Therefore, ECMO was administered on day 7. Controlling coagulation function to maintain ECMO therapy was challenging. Nafamostat mesylate and cryoprecipitate were administered to treat the hypercoagulative status and severe hypofibrinogenemia, respectively. Since coagulopathy and her respiratory state improved, the ECMO therapy was terminated on day 15. CONCLUSIONS We report a case of severe COVID-19 pneumonia in a pregnant woman urgently treated with ECMO in the postpartum period. Thus, this case highlights the importance of close monitoring and appropriate medical care for pregnant women with severe COVID-19 pneumonia.
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http://dx.doi.org/10.12659/AJCR.927521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603798PMC
October 2020

Comparative analysis demonstrates cell type-specific conservation of SOX9 targets between mouse and chicken.

Sci Rep 2019 08 29;9(1):12560. Epub 2019 Aug 29.

Department of Systems BioMedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

SRY (sex-determining region Y)-box 9 (SOX9) is a transcription factor regulating both chondrogenesis and sex determination. Among vertebrates, SOX9's functions in chondrogenesis are well conserved, while they vary in sex determination. To investigate the conservation of SOX9's regulatory functions in chondrogenesis and gonad development among species, we performed chromatin immunoprecipitation sequencing (ChIP-seq) using developing limb buds and male gonads from embryos of two vertebrates, mouse and chicken. In both mouse and chicken, SOX9 bound to intronic and distal regions of genes more frequently in limb buds than in male gonads, while SOX9 bound to the proximal upstream regions of genes more frequently in male gonads than in limb buds. In both species, SOX palindromic repeats were identified more frequently in SOX9 binding regions in limb bud genes compared with those in male gonad genes. The conservation of SOX9 binding regions was significantly higher in limb bud genes. In addition, we combined RNA expression analysis (RNA sequencing) with the ChIP-seq results at the same stage in developing chondrocytes and Sertoli cells and determined SOX9 target genes in these cells of the two species and disclosed that SOX9 targets showed high similarity of targets in chondrocytes, but not in Sertoli cells.
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http://dx.doi.org/10.1038/s41598-019-48979-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715657PMC
August 2019

Comprehensive proteome analysis of brush border membrane fraction of ileum of ezrin knockdown mice.

Biomed Res 2016 ;37(2):127-39

Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University.

Ezrin is an actin binding protein which cross-links membrane proteins with cytoskeleton directly or indirectly via PDZ domain-containing scaffold proteins. It is mainly expressed at the brush border membrane (BBM) of gastrointestinal tracts, and is involved in the construction of microvilli structure and the functional expression of membrane protein complexes at the cell surface. To precisely study the roles of ezrin on the expression of membrane proteins at the cell surface, here we prepared the BBM fractions of ileums from the wild-type and ezrin-knockdown (Vil2(kd/kd)) mice, analyzed them by mass spectrometry, and compared their proteomic patterns. Totally 313 proteins were identified in the BBM fractions. Several transport proteins, cytoskeleton-associated proteins, and trafficking proteins were up- or down-regulated in the BBM fraction of the ileum in the Vil2(kd/kd) mice. Among them, the expressions of i) Na(+)/H(+) exchanger regulatory factor 1 (a PDZ domain-containing scaffold protein), ii) sodium monocarboxylate transporter 1, which contains a PDZ domain-binding motif at their carboxy-terminal, and iii) chloride intracellular channel protein 5 were down-regulated at the BBM fraction of the ileum in the Vil2(kd/kd) mice, suggesting that ezrin is involved in their expression in the BBM.
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http://dx.doi.org/10.2220/biomedres.37.127DOI Listing
January 2017

Effects of ezrin knockdown on the structure of gastric glandular epithelia.

J Physiol Sci 2016 Jan 2;66(1):53-65. Epub 2015 Sep 2.

Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.

Ezrin, an adaptor protein that cross-links plasma membrane-associated proteins with the actin cytoskeleton, is concentrated on apical surfaces of epithelial cells, especially in microvilli of the small intestine and stomach. In the stomach, ezrin is predominantly expressed on the apical canalicular membrane of parietal cells. Transgenic ezrin knockdown mice in which the expression level of ezrin was reduced to <7% compared with the wild-type suffered from achlorhydria because of impairment of membrane fusion between tubulovesicles and apical membranes. We observed, for the first time, hypergastrinemia and foveolar hyperplasia in the gastric fundic region of the knockdown mice. Dilation of fundic glands was observed, the percentage of parietal and chief cells was reduced, and that of mucous-secreting cells was increased. The parietal cells of knockdown mice contained dilated tubulovesicles and abnormal mitochondria, and subsets of these cells contained abnormal vacuoles and multilamellar structures. Therefore, lack of ezrin not only causes achlorhydria and hypergastrinemia but also changes the structure of gastric glands, with severe perturbation of the secretory membranes of parietal cells.
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http://dx.doi.org/10.1007/s12576-015-0393-4DOI Listing
January 2016

Progression risk assessments of individual non-invasive gastric neoplasms by genomic copy-number profile and mucin phenotype.

BMC Med Genomics 2015 Feb 18;8. Epub 2015 Feb 18.

Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Otsu, 520-2192, Japan.

Background: Early detection and treatment of non-invasive neoplasms can effectively reduce the incidence of advanced gastric carcinoma (GC), but only when the lineage is continuous between non-invasive and advanced tumours. Although a fraction of non-invasive neoplasms progress to invasive GC, it is difficult to identify individual progression-prone non-invasive neoplasms. To classify non-invasive gland-forming gastric neoplasms into clusters of different levels of progression risk, we applied mucin phenotyping and genomic DNA microarray analyses to intramucosal gland-forming gastric neoplasms.

Methods: Formalin-fixed, paraffin-embedded tissues from 19 non-invasive and 24 invasive gland-forming neoplasms were obtained via endoscopic submucosal dissection or surgical excision. According to the Vienna classification, intramucosal neoplasms were classified as low-grade or high-grade non-invasive neoplasms (LGNs [category 3] and HGNs [category 4], respectively) or invasive carcinomas (intramucosal GCs and mucosal parts of submucosal or deeper GCs [category 5]). Neoplastic lesions were characterized by mucin phenotypes determined using monoclonal antibodies against MUC2, MUC5AC, MUC6, and CD10. Genomic DNA samples from mucosal neoplasms were subjected to array-based comparative genomic hybridization and subsequent unsupervised, hierarchical clustering with selected large-sized genes.

Results: There was no significant difference in mucin phenotype between HGNs/LGNs and invasive carcinomas. The clustering classified samples into stable, unstable, and intermediate. The histological tumour grade or mucin phenotype of non-invasive neoplasms did not correlate with the clustering results. Each cluster may represent an independent lineage of different outcome because the size distribution of non-invasive tumours among the 3 clusters almost overlapped. In contrast, the unstable cluster alone included invasive carcinomas.

Conclusions: These findings suggest that the outcome of individual tumours is not stochastically determined but can be predicted from the genomic copy-number profile even at the non-invasive stage. Non-invasive neoplasms of the unstable clusters, which accounted for 21% of non-invasive neoplasms, may progress to invasive carcinomas, whereas those of stable cluster may not.
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http://dx.doi.org/10.1186/s12920-015-0080-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346124PMC
February 2015

A prospective, randomized comparison between single- and multiple-injection techniques for ultrasound-guided subgluteal sciatic nerve block.

Anesth Analg 2014 Dec;119(6):1442-8

From the Department of Anesthesiology, Shimane University School of Medicine, Izumo City, Japan.

Background: It is believed that local anesthetic injected to obtain circumferential spread around nerves produces a more rapid onset and successful blockade after some ultrasound-guided peripheral nerve blocks. However, evidence demonstrating this point is limited only to the popliteal sciatic nerve block, which is relatively easy to perform by via a high-frequency linear transducer. In the present study, we tested the hypothesis that multiple injections of local anesthetic to make circumferential spread would improve the rate of sensory and motor blocks compared with a single-injection technique for ultrasound-guided subgluteal sciatic nerve block, which is considered a relatively difficult block conducted with a low-frequency, curved-array transducer.

Methods: Ninety patients undergoing knee surgery were divided randomly into 2 groups to receive the ultrasound-guided subgluteal approach to sciatic nerve block with 20 mL of 1.5% mepivacaine with epinephrine. For group M (the multiple-injection technique), the local anesthetic was injected to create circumferential spread around the sciatic nerve without limitation on the number of needle passes. For group S (the single-injection technique), the number of needle passes was limited to 1, and the local anesthetic was injected to create spread along the dorsal surface of the sciatic nerve, during which no adjustment of the needle tip was made. Sensory and motor blockade were assessed in double-blind fashion for 30 minutes after completion of the block. The primary outcome was sensory blockade of all sciatic components tested, including tibial, superficial peroneal, and sural nerves at 30 minutes after injection.

Results: Data from 86 patients (43 in each group) were analyzed. Block execution took more time for group M than group S. The proportion of patients with complete sensory blockade of all sciatic components at 30 minutes after injection was significantly larger for group M than group S (41.9% vs 16.3%, P = 0.018). Complete motor blockade of foot and toes extension also was observed more frequently in group M than in group S (67.4% vs 34.9%, P = 0.005 and 51.2% vs 25.6%, P = 0.027, respectively).

Conclusions: When ultrasound-guided subgluteal sciatic nerve block is conducted, multiple injections of local anesthetic to make a circumferential spread around the sciatic nerve improve the rate of sensory and motor blocks compared with a single injection.
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http://dx.doi.org/10.1213/ANE.0000000000000462DOI Listing
December 2014

Elevated levels of angiopoietin-2 as a biomarker for respiratory failure after cardiac surgery.

J Cardiothorac Vasc Anesth 2014 Oct 11;28(5):1293-301. Epub 2014 Jul 11.

Department of Anesthesiology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.

Objectives: Angiopoietin-1 and angiopoietin-2 are important factors in regulating endothelial vascular permeability. This study evaluated perioperative changes in serum levels of angiopoietin-1 and -2 in patients undergoing cardiac surgery.

Design: Measurement of serum levels of angiopoietin-1 and angiopoietin-2 in samples collected during a previously conducted prospective, multicenter, observational study.

Setting: Three university hospitals.

Participants: Eighty-four adult patients undergoing cardiac surgery.

Intervention: Serum levels of angiopoietins were measured at baseline, immediately after surgery, and the day after surgery (POD-1).

Measurements And Main Results: Serum levels of angiopoietin-2 were elevated by POD-1 (median 3.3 ng/mL, interquartile range [IQR] 2.5-4.6 ng/mL) compared with baseline (median 1.6 ng/mL, IQR 1.3-2.1 ng/mL, p < 0.0001), and angiopoietin-1 levels were decreased immediately after surgery (baseline median 23.2 ng/mL, IQR 10.2-32.8 ng/mL; postoperative median 8.0 ng/mL, IQR 1.5-13.2 ng/mL, p<0.0001). Angiopoietin-2 levels on POD-1 in patients undergoing off-pump coronary artery bypass grafting were significantly lower than those in patients undergoing aortic surgery (p = 0.0009) and valve surgery (p = 0.008). Angiopoietin-2 levels on POD-1 had a predictive performance of the area under the curve (AUC) of the receiver operating characteristic curve 0.74 for mechanical ventilation>3 days. Angiopoietin-1 levels and the angiopoietin-2/angiopoietin-1 ratio showed lower predictive performance (AUC values 0.58 and 0.68, respectively).

Conclusions: Angiopoietin-2 serum levels were elevated after cardiac surgery. Elevated angiopoietin-2 had a good predictive performance for respiratory failure after cardiac surgery, perhaps reflecting the severity of lung dysfunction related to postoperative increases in vascular permeability.
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http://dx.doi.org/10.1053/j.jvca.2014.03.004DOI Listing
October 2014

Continuous taurocholic acid exposure promotes esophageal squamous cell carcinoma progression due to reduced cell loss resulting from enhanced vascular development.

PLoS One 2014 14;9(2):e88831. Epub 2014 Feb 14.

Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Shiga, Japan.

Background: Refluxogenic effects of smoking and alcohol abuse may be related to the risk of esophageal squamous cell carcinoma (ESCC). The present study attempts to clarify the effects of continuous taurocholic acid (TCA) exposure, which is neither mutagenic nor genotoxic, on ESCC progression.

Methods: A squamous carcinoma cell line (ESCC-DR) was established from a tumor induced in a rat model of gastroduodenal reflux. ESCC-DR cells were incubated with 2 mM TCA for ≥2 months. The effects of continuous TCA exposure were evaluated in vitro on cell morphology, growth, and invasion and in vivo on xenograft tumor growth in nude mice. Moreover, the mean level of secreted transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) proteins in cell culture supernatants and mRNA synthesis of TGF-β1 and VEGF-A of ESCC cells were measured. The angiogenic potential was further examined by a migration assay using human umbilical vein endothelial cells (HUVECs).

Results: Continuous TCA exposure induced marked formation of filopodia in vitro. Expression levels of angiogenic factors were significantly higher in the cells treated with TCA than in control cells. Tumor xenografts derived from cells pre-exposed to TCA were larger and more vascularized than those derived from control cells. In addition, TCA exposure increased HUVEC migration.

Conclusion: Continuous TCA exposure enhanced ESCC progression due to reduced cell loss in vivo. Cell loss was inhibited by TCA-induced vascular endothelial cell migration, which was mediated by TGF-β1 and VEGF-A released from ESCC cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088831PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925151PMC
October 2014

Precursor-derived versus de-novo carcinogenesis depends on lineage-specific mucin phenotypes of intramucosal gland-forming gastric neoplasms.

Histopathology 2013 Nov 19;63(5):616-29. Epub 2013 Aug 19.

Department of Pathology, Division of Molecular Diagnostic Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan; Department of Internal Medicine, Division of Gastroenterology and Hematology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Aims: To clarify the lineage-specific carcinogenesis of gland-forming gastric neoplasms, by characterizing mucin phenotypes and proliferation patterns immunohistochemically using monoclonal antibodies against MUC2, MUC5AC, MUC6, CD10 and Ki67.

Methods And Results: We analysed 49 gland-forming intramucosal neoplasms, including 15 non-invasive low-grade neoplasms (group A), 10 non-invasive high-grade neoplasms (group B) and 24 intramucosal adenocarcinomas (group C). The mode of gland-forming gastric carcinoma development was different between the intestinal and gastric lineages. The pure intestinal-type accounted for 93% of group A, 50% of group B and 4.2% of group C tumours. A zonal pattern of cell proliferation was well retained in group A tumours and was lost size-dependently in group B tumours. These findings suggest that non-invasive low-grade neoplasms of the intestinal lineage progress to non-invasive high-grade neoplasms, but rarely to intramucosal adenocarcinomas. In tumours of the gastric lineage, which exhibited pure gastric or mixed phenotypes, the polarity of cell proliferation and differentiation was well retained in small (≦5 mm) tumours but was lost in larger tumours in groups B and C.

Conclusions: Intramucosal adenocarcinomas of the gastric lineage may often arise de novo, develop in the proper gastric mucosa, and are partially derived from non-invasive high-grade neoplasms.
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http://dx.doi.org/10.1111/his.12208DOI Listing
November 2013

Mechanisms underlying cancer progression caused by ezrin overexpression in tongue squamous cell carcinoma.

PLoS One 2013 24;8(1):e54881. Epub 2013 Jan 24.

Department of Pathology, Division of Molecular Diagnostic Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Background: Ezrin is a member of the ezrin, radixin, and moesin family that provides a functional link between the plasma membrane and the cortical actin cytoskeleton. A correlation between ezrin overexpression and aggressive cancer behavior has been recently reported in various tumor types. However, its roles in the mechanisms underlying progression of tongue squamous cell carcinoma (SCC) are unclear.

Method: We used human tongue SCC and noncancerous tissue microarrays to immunohistochemically analyze the ezrin expression level and its relationship with proliferative activity. The human tongue SCC cell line HSC-3 was used to determine the effects of ezrin RNA interference (RNAi) on cancer cells during MTT; wound healing and invasion assays; immunofluorescence of the actin cytoskeleton; and western blotting of E-cadherin, N-cadherin, β-catenin, and the active and total RhoA/Rac1/cdc42.

Results: Ezrin was overexpressed in 46.4% of the tumors examined in human tongue SCC tissue microarrays. Ezrin expression was correlated with the Ki-67 index. Ezrin depletion by RNAi in the HSC-3 cells significantly reduced cell proliferation, migration, and invasiveness and disturbed actin reorganization during podia formation. Its effects on RhoA/Rac1/cdc42 expression were not significant, whereas it enhanced E-cadherin and β-catenin expression and decreased N-cadherin expression.

Conclusions: Ezrin is often overexpressed in primary tongue SCCs and may have an important role in their growth, migration, and invasiveness possibly via its relationship with the E-cadherin/β-catenin complex and the cadherin switch. Thus, ezrin could be a therapeutic target in tongue SCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054881PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554659PMC
September 2013

Retrospective analysis of spontaneous recovery from neuromuscular blockade produced by empirical use of rocuronium.

J Anesth 2011 Dec 21;25(6):845-9. Epub 2011 Sep 21.

Department of Anesthesiology, Tokyo Medical and Dental University, Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Purpose: A train-of-four ratio (TOF ratio) of >0.9 should be the clinical cut-off to avoid residual paralysis. However, it is not rare to extubate patients without measurement of the TOF ratio, although the safe interval from the last administration of rocuronium assuring a TOF ratio of >0.9 has not been established in the daily clinical setting. In this study, to estimate the safe interval to avoid residual paralysis, we retrospectively selected patients in whom the TOF ratio was measured during remifentanil administration before extubation, and we studied the characteristics of recovery from the neuromuscular blockade produced by the empirical use of rocuronium.

Methods: Patients undergoing surgery under general anesthesia with sevoflurane and remifentanil were studied (n = 134). Rocuronium was administered at 0.7-1.0 mg/kg for tracheal intubation, and repeated bolus administration (10 mg) or continuous infusion (15-25 mg/h) was performed by the anesthesiologists in charge of the patient to maintain intraoperative paralysis. At the end of the surgery, the TOF ratio was measured, during remifentanil infusion and the contribution of clinical parameters to spontaneous recovery from the rocuronium-induced paralysis was studied by multivariate logistic regression analyses.

Results: Spontaneous recovery from rocuronium-induced paralysis within 2 h after the last administration of rocuronium varied among the patients. Multivariate logistic regression analyses showed that age (P = 0.002) and time elapsed from the last administration of rocuronium (P < 0.0001) significantly contributed to TOF recovery, and elderly patients demonstrated significantly slower recovery.

Conclusion: Because of the large variation in the recovery from rocuronium-induced paralysis, TOF-based evaluation of residual paralysis is essential to determine the appropriate indication for reversal, especially for elderly patients.
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http://dx.doi.org/10.1007/s00540-011-1229-xDOI Listing
December 2011

Down-regulation of FXYD3 is induced by transforming growth factor-β signaling via ZEB1/δEF1 in human mammary epithelial cells.

Biol Pharm Bull 2011 ;34(3):324-9

Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525–8577, Japan.

FXYD3, a regulator of Na, K-ATPase, was identified as an mRNA overexpressed in murine breast cancers induced by neu oncogene, which had inactivated transforming growth factor (TGF)-β signaling due to the defect of TGF-β receptor I (TβRI) expression. To elucidate whether the expression of FXYD3 mRNA was regulated by TGF-β signaling, we used a normal human mammary epithelial cell line, MCF-10A which responds to TGF-β and tumor necrosis factor (TNF)-α, followed by induction of epithelial-to-mesenchymal transition (EMT). Here, we showed that FXYD3 at plasma membrane in epithelial state of MCF-10A cells was decreased by treatment of TGF-β and TNF-α. The repression of FXYD3 mRNA induced by TGF-β and TNF-α in MCF-10A cells was abolished by TβRI inhibitor or Smad3 inhibitor, but not by small interfering RNA (siRNA) for Smad2. In addition, expression level of FXYD3 mRNA was up-regulated by the silencing of ZEB1/δEF1 transcriptional repressor which was a down-stream target gene of TGF-β and an inducer of EMT. On the other hand, expression level and cellular localization of E-cadherin and N-cadherin were not changed by siRNA for FXYD3 in MCF-10A and human breast cancer MCF-7 cells. These results suggest that FXYD3 is a target gene of TGF-β signaling through ZEB1/δEF1, but is not directly involved in EMT.
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http://dx.doi.org/10.1248/bpb.34.324DOI Listing
November 2011

Initiation of malignancy by duodenal contents reflux and the role of ezrin in developing esophageal squamous cell carcinoma.

Cancer Sci 2010 Mar 15;101(3):624-30. Epub 2009 Dec 15.

Department of Pathology, Shiga University of Medical Science, Shiga, Japan.

Gastroesophageal reflux has recently been implicated as a causative factor in upper aerodigestive tract carcinogenesis. Esophageal squamous cell carcinomas (ESCCs) have developed in duodenal-content reflux animals without any known carcinogen present. We established a cell line, designated ESCC-DR, from a thoracic metastatic tumor in a reflux animal. To gain insight into the genomic alterations associated with duodenal content reflux-induced carcinogenesis, we first performed comparative genomic hybridization using an Agilent rat 244K array in ESCC-DR and identified many chromosomal gains and losses. Of the many genes identified, we detected an interesting ezrin amplicon that has been recently reported in human ESCC. Ezrin, which cross-links the cytoskeleton and plasma membrane, is involved in the growth and metastatic potential of cancer cells. Overexpression of ezrin protein in ESCC-DR was confirmed by Western blotting. We also compared ezrin protein expression levels and patterns in hyperplastic, dysplastic, ESCC, and metastatic sites developed in two distinct reflux models using immunohistochemistry. Immunohistochemical staining of ezrin revealed overexpression in the nucleus, and the cytoplasm as well as plasma membrane of ESCC cells. Phosphorylated ERM (ezrin, radixin, moesin) was expressed at the leading edge, or invasive front, of larger metastatic sites. Taken together, duodenal reflux has a great potential for initiating malignancy, and thus likely plays a role in development of ESCC. Ezrin probably influences the growth and invasiveness of ESCC cells, and phosphorylation is only required in metastatic behavior of tumor cells at the leading edge and invasive front.
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http://dx.doi.org/10.1111/j.1349-7006.2009.01470.xDOI Listing
March 2010

FXYD3 protein involved in tumor cell proliferation is overproduced in human breast cancer tissues.

Biol Pharm Bull 2009 Jul;32(7):1148-54

Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University.

FXYD3, also known as Mat-8 (Mammary tumor 8 kDa), is one of mRNAs highly expressed in mouse and human breast cancers. Here, we newly found that FXYD3 protein was also overexpressed in human breast cancer specimens; invasive ductal carcinomas and intra-ductal carcinomas, whereas its expression was low in benign lesion specimens; mastopathy, fibroadenoma and phyllodes tumors. Although human FXYD3 has two isoforms (shorter FXYD3a and longer FXYD3b), there have been no reports in which these two mRNAs were separately quantified. Here, we found that FXYD3a mRNA is a major transcript product expressed in human normal tissues as well as in breast, colon, stomach and pancreas cancer cell lines. In addition, expression level of FXYD3b was much lower than that of FXYD3a in these cancer cell lines. Cell proliferation rate of MCF-7 breast cancer cell line was drastically decreased when FXYD3a and 3b mRNAs were suppressed by the small interfering RNA. These results suggest that FXYD3a protein is highly expressed in breast cancers, and responsible for cancer cell proliferation.
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http://dx.doi.org/10.1248/bpb.32.1148DOI Listing
July 2009

Penile apoptosis in association with p53 under lack of testosterone.

Urol Res 2004 Feb 18;32(1):9-13. Epub 2003 Dec 18.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho Mizuho-ku, Nagoya, Japan.

It is known that testosterone deficiency induces apoptosis in the prostate and that p53 protein is involved in this apoptosis. Therefore, p53 protein may also be involved in apoptosis induction in a testosterone-deficient state in the penis. In this study, we investigated whether castration and chemical castration induce apoptosis at penile tissue in rats, and whether p53 protein is involved in this apoptosis. Male SD rats aged 8 weeks were divided into four groups: 1) the Control group; 2) the Castration group; 3) the Estrogen group, in which rats received betaestradiol 17-(beta-D-glucuronide) injection of 500 microg/body/day; and 4) the LH-RH group, in which rats received LH-RH analogue (leuprorelin acetate) injection of 2 mg/kg. The rats were sacrificed after treatment on days 1, 3, 5, 14, and 28 by cervical dislocation. Apoptotic cells and p53 protein-positive cells were observed on the 5th day after treatment and thereafter in all castration, estrogen, and LH-RH groups. These findings showed that both castration and chemical castration induced p53 protein in vascular endothelial cells in the corpus cavernosus during the process of losing testosterone. It was also suggested that in such states, apoptosis is induced in vascular endotherial cells in the corpus cavernosus.
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http://dx.doi.org/10.1007/s00240-003-0358-6DOI Listing
February 2004
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