Publications by authors named "Toshihiro Yorozuya"

54 Publications

Hemodynamic deterioration due to increased anterior and posterior cardiac compression during posterior spinal fusion for scoliosis with pectus excavatum.

SAGE Open Med Case Rep 2022 10;10:2050313X221090848. Epub 2022 May 10.

Department of Anesthesia and Perioperative Medicine, Graduate School of Medicine, Ehime University, Toon, Japan.

Hemodynamics may deteriorate during the perioperative period when performing posterior spinal fusion in patients with pectus excavatum and scoliosis. A 13-year-old teenager diagnosed with Marfan syndrome had thoracic scoliosis and pectus excavatum. Thoracic scoliosis was convex to the right, and a right ventricular inflow tract stenosis was observed due to compression induced by the depressed sternum. The patient underwent T3-L4 posterior spinal fusion surgery for scoliosis. Deterioration of hemodynamics was observed when the patient was placed in the prone position or when the thoracic spine was corrected to the left front. Postoperative computed tomography examination showed that the mediastinal space was narrowed due to the corrected thoracic spine. Special attention should be paid in the following cases: (1) severe pectus excavatum, (2) right ventricular inflow tract compression due to depressed sternum on the left side, (3) correction of the thoracic spine on the left front, (4) long-term surgery, and (5) risk of massive bleeding. In some cases, pectus excavatum surgery should be prioritized.
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http://dx.doi.org/10.1177/2050313X221090848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096201PMC
May 2022

Enhanced recovery from fulminant myocarditis by treatment with the combined use of the Impella left ventricular assist device with extracorporeal membrane oxygenation: a case series.

JA Clin Rep 2022 Feb 27;8(1):15. Epub 2022 Feb 27.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Background: We experienced two adult cases of fulminant myocarditis with severe cardiogenic shock where Impella left ventricular assist device [left ventricle (LV)-Impella] was concomitantly used with venoarterial extracorporeal membrane oxygenation (V-A ECMO).

Case Presentation: A 67-year-old man and a 49-year-old man with fulminant myocarditis were transferred to our hospital with mechanical support of V-A ECMO and IABP. Impella 5.0 and Impella CP were implanted 21 h and 17 h after establishing V-A ECMO for each case. Within 1 week, the patients' LV function progressively improved. Then the Impellas were withdrawn after discontinuing V-A ECMO. They were discharged from the intensive care unit within the following 8 days.

Conclusions: The optimal introducing timing of LV-Impella is not currently precise. However, this case report suggests that the initiation of LV-Impella within at least 24 h after establishing V-A ECMO may be acceptable for the recovery of cardiac function.
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http://dx.doi.org/10.1186/s40981-022-00502-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882485PMC
February 2022

Glucocorticoid imprints a low glucose metabolism onto CD8 T cells and induces the persistent suppression of the immune response.

Biochem Biophys Res Commun 2022 01 17;588:34-40. Epub 2021 Dec 17.

Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon City, Ehime, 791-0295, Japan; Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan; Department of Translational Immunology, Translational Research Center, Ehime University Hospital, Shitsukawa, Toon City, Ehime, 791-0295, Japan. Electronic address:

Glucocorticoids (GCs), immunosuppressive, and anti-inflammatory agents have various effects on T cells. However, the long-term influence of GCs on the T cell-mediated immune response remain to be elucidated. We demonstrated that the administration of GC during the TCR-mediated activation phase induced long-lasting suppression of glycolysis, even after the withdrawal of GC. The acquisition of the effector functions was inhibited, while the expression of PD-1 was increased in CD8 T cells activated in the presence of GC. Furthermore, adoptive transfer experiments revealed that GC-treated CD8 T cells reduced memory T cell formation and anti-tumor activity. These findings reveal that GCs have long-lasting influence on the T cell-mediated immune response via modulation of T cell metabolism.
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http://dx.doi.org/10.1016/j.bbrc.2021.12.050DOI Listing
January 2022

Perioperative management of emergent cesarean section in a patient with peripartum cardiomyopathy and orthopnea: a case report.

J Int Med Res 2021 Dec;49(12):3000605211063077

Department of Anesthesia and Perioperative Medicine, 38050Ehime University Graduate School of Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Perioperative management of pregnant women with heart failure is difficult. Management of anesthesia in pregnant women is especially difficult because all of the currently available choices present challenges. We report a patient with peripartum cardiomyopathy (PPCM) who required an emergent cesarean section and discuss the possible tactics for managing anesthesia. A 40-year-old primipara with severe cardiac and respiratory failure required an emergent cesarean section at 39 gestational weeks. Her left ventricular ejection fraction was between 10% and 15%, and she had orthopnea. General anesthesia was planned after inserting sheaths for percutaneous cardiopulmonary support from the femoral artery and vein. However, when the patient was asked to lie down on the operation bed, she panicked and resisted because of labor pain and dyspnea. Therefore, anesthesia was induced instead of the initial plan. Finally, we successfully managed the anesthesia and delivered the newborn. There are no alternatives to general anesthesia in patients with PPCM presenting with orthopnea. Anesthesia induction in the supine position is impossible in such patients owing to dyspnea. Anesthesia should be started with light sedation in the sitting position, and ketamine or low-dose remifentanil may be an option to maintain maternal hemodynamics and prevent neonatal asphyxia.
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http://dx.doi.org/10.1177/03000605211063077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678898PMC
December 2021

Treatment and prognosis of patients with both cancer and impaired decision-patient with both cancer and dementia making as a symptom of dementia.

Geriatr Gerontol Int 2021 Dec 15;21(12):1105-1110. Epub 2021 Oct 15.

Department of Clinical Oncology, Ehime University Graduate School of Medicine, Toon, Japan.

Aim: In our aging society, the number of patients with both cancer and dementia has recently been increasing. One of the major clinical questions is whether patients with dementia could receive appropriate cancer treatment. The purpose of this study is to know the prognosis of patients with both cancer and impaired decision-making as a symptom of dementia, and to discuss the proper cancer treatment of the patients with dementia.

Methods: Patients newly diagnosed with both cancer and impaired decision-making as a symptom of dementia at Ehime University Hospital between January 2010 and December 2016 were reviewed. The data of patients with cancer were retrospectively analyzed using an electronic medical record system.

Results: In total, 9354 cases were diagnosed with cancer in the Ehime University Hospital over 7 years, and only 105 (1.1%) cases with impaired decision-making as a symptom of dementia were recorded by medical professionals, probably due to poor attention to the cognitive functions of patients with cancer. Analysis of the cancer prognosis of these patients showed that a better prognosis was seen in patients with any therapeutic interventions than in those with no treatment for the cancer itself. However, the prognosis of patients was not significantly different between standard and non-standard treatments.

Conclusions: This study suggests that the poor interest of medical professionals in the cognitive function of patients with cancer at the time of diagnosis of cancer and the lack of any guidelines for patients with both cancer and dementia are major problems in our aging society. Geriatr Gerontol Int 2021; 21: 1105-1110.
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http://dx.doi.org/10.1111/ggi.14292DOI Listing
December 2021

Independent Predicting Factors for Subcutaneous Emphysema Associated with Robotic-Assisted Laparoscopic Radical Prostatectomy: A Retrospective Single-Center Study.

J Clin Med 2021 Jul 4;10(13). Epub 2021 Jul 4.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Toon 791-0295, Ehime, Japan.

Objectives: Subcutaneous emphysema (SCE) is a complication associated with laparoscopic surgery. Severe SCE complicated by excessive hypercarbia may afford detrimental effects in surgical patients with cardiac dysfunction. Robotic-assisted laparoscopic radical prostatectomy (RALP) has several predisposing factors that contribute to SCE. The main purpose of our single-center retrospective study was to determine the preoperative and intraoperative predicting factors for SCE associated with RALP and to determine the actual incidence of SCE.

Methods: In total, 229 adult male patients underwent standardized RALP for prostate cancer over the period of 1 May 2016 to 31 October 2018 at the Ehime University Hospital. We reviewed electronic clinical records for individual characteristics including age, body weight, height, coexisting disorders, preoperative ASA physical status, and the length of postoperative hospital stay. We also reviewed surgical and anesthetic records for the operation time, anesthetic method, and the partial pressure of end-tidal CO (PetCO) during RALP. To determine the presence of SCE, we examined supine chest X-rays obtained after the completion of surgery.

Results: We found 55 cases (24.0%) of SCE. Multiple logistic regression analysis showed that a BMI < 25 kg/m (OR: 3.0, 95% CI: 1.25-7.26) and a maximum value of PetCO of 46 mmHg or greater (OR: 23.3, 95% CI: 8.22-66.1) were independent predicting factors for SCE.

Conclusion: These two predicting factors may be helpful to recognize the occurrence of SCE. Anesthesiologists should protect against SCE progression with the earlier detection of SCE for safe anesthetic management in patients undergoing RALP.
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http://dx.doi.org/10.3390/jcm10132985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269410PMC
July 2021

Takotsubo Cardiomyopathy Induced by Very Low-Dose Epinephrine Contained in Local Anesthetics: A Case Report.

Am J Case Rep 2021 Jun 26;22:e932028. Epub 2021 Jun 26.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

BACKGROUND Takotsubo cardiomyopathy is a reversible left ventricular dysfunction triggered by emotional or physical stress. Perioperatively, takotsubo cardiomyopathy is sometimes induced by various psychological factors, such as stress from surgery, and non-psychological factors, such as epinephrine misinjection. This report describes a case of takotsubo cardiomyopathy induced by the administration of very low-dose epinephrine contained in a local anesthetic. CASE REPORT A 78-year-old woman with mycosis in the maxillary sinus was scheduled to undergo endoscopic sinus surgery. After the submucosal injection of 3 mL of local anesthetic (lidocaine, 0.5%; epinephrine, 1: 200 000) immediately before the incision, her heart rate and blood pressure reached 135 beats per min and 254/185 mmHg, respectively, inducing ventricular tachycardia. After receiving 50 mg of lidocaine, her cardiac rhythm resumed a normal sinus rhythm, without cardioversion. As her hemodynamics stabilized, the surgical procedure began as planned. Postoperative electrocardiography, echocardiography, and coronary arteriography demonstrated takotsubo cardiomyopathy. Subsequently, her cardiac movement gradually improved, and she was discharged from the hospital on postoperative day 9. CONCLUSIONS To the best of our knowledge, this is the first reported case in which a very small amount of epinephrine (0.015 mg) induced takotsubo cardiomyopathy. Therefore, epinephrine should be used cautiously, especially in the nasal mucosa, vaginal mucosa, and uterus, where blood flow is relatively high. If unexpected hemodynamic alterations and ST-segment abnormalities occur after epinephrine administration, asymptomatic takotsubo cardiomyopathy should be considered.
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http://dx.doi.org/10.12659/AJCR.932028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244375PMC
June 2021

Disseminated intravascular coagulation as a complication of bursitis: angiogenesis and repetitive bleeding as potential factors for disseminated intravascular coagulation: a case report.

J Med Case Rep 2021 Apr 10;15(1):155. Epub 2021 Apr 10.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan.

Background: Malignant tumors, such as acute leukemia and solid cancers, frequently cause disseminated intravascular coagulation. However, cases of disseminated intravascular coagulation as a complication of bursitis were not reported previously.

Case Presentation: A 72-year-old Japanese woman was scheduled to undergo resection of a rapidly growing subcutaneous tumor-like lesion on her left back. Preoperative blood tests suggested disseminated intravascular coagulation. The resected lesion was cystic tumor containing a hematoma. After the operation, the patient completely recovered from disseminated intravascular coagulation, indicating that disseminated intravascular coagulation in this case was caused by the tumor. Pathological examination of the resected tumor revealed considerable fibrin deposition and angiogenesis on the cyst wall, which was presumably a response to inflammation and indicated presence of repetitive intratumoral bleeding, subsequently leading to a diagnosis of chronic hemorrhagic bursitis.

Conclusions: Clinicians should note that, despite being benign, soft-tissue tumors accompanied by inflammation with angiogenesis and repetitive intratumoral bleeding can cause disseminated intravascular coagulation, albeit rarely.
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http://dx.doi.org/10.1186/s13256-021-02773-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035724PMC
April 2021

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems.

Cells 2020 09 21;9(9). Epub 2020 Sep 21.

Department of Molecular and cellular Physiology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.

Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes.
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http://dx.doi.org/10.3390/cells9092132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563796PMC
September 2020

T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses.

Commun Biol 2020 07 24;3(1):394. Epub 2020 Jul 24.

Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon City, Ehime, 791-0295, Japan.

Although the important roles of glycolysis in T cells have been demonstrated, the regulatory mechanism of glycolysis in activated T cells has not been fully elucidated. Furthermore, the influences of glycolytic failure on the T cell-dependent immune response in vivo remain unclear. We therefore assessed the role of glycolysis in the T cell-dependent immune response using T cell-specific Pgam1-deficient mice. Both CD8 and CD4 T cell-dependent immune responses were attenuated by Pgam1 deficiency. The helper T cell-dependent inflammation was ameliorated in Pgam1-deficient mice. Glycolysis augments the activation of mTOR complex 1 (mTORC1) and the T-cell receptor (TCR) signals. Glutamine acts as a metabolic hub in activated T cells, since the TCR-dependent increase in intracellular glutamine is required to augment glycolysis, increase mTORC1 activity and augment TCR signals. These findings suggest that mTORC1, glycolysis and glutamine affect each other and cooperate to induce T cell proliferation and differentiation.
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http://dx.doi.org/10.1038/s42003-020-01122-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382475PMC
July 2020

A case report of thrombotic complete obstruction of the ascending aorta as a complication of Venoarterial extracorporeal membrane oxygenation support: steps to prevent thrombosis.

J Cardiothorac Surg 2020 Jul 23;15(1):185. Epub 2020 Jul 23.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential device in the field of emergency and intensive-care medicine. However, long-term use of VA-ECMO has various severe complications, including thrombosis.

Case Presentation: A 60-year-old man underwent his third aortic root replacement using a homograft because of infectious endocarditis. Although the operation was difficult because of severe adhesion caused by the two previous interventions, aortic root replacement using a homograft was performed. At the time of withdrawal from cardiopulmonary bypass, the maintenance of hemodynamics was difficult because of bleeding from the surgical site, leading to hypovolemic shock. Cardiac function subsequently deteriorated; therefore, VA-ECMO was established and the operation was finished. Three days later, thrombus was formed inside the homograft and completely occluded ascending aorta. Evacuation of hematoma was performed, however, cardiac function was not ameliorated. Eventually, the patient had brain infarction and died. To prevent thrombus formation in very severe low cardiac output cases under VA-ECMO management after surgery, to prevent the stagnation of the blood flow from VA-ECMO will be necessary because anticoagulant therapy will be difficult. Impella ventricular assist device which is recently used widely generates anterograde blood flow and effectively prevents stagnation.

Conclusions: To prevent thrombus formation in cases of very severe low cardiac output, Impella® should be combinatorially introduced from the beginning of VA-ECMO establishment to prevent thrombosis.
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http://dx.doi.org/10.1186/s13019-020-01239-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379763PMC
July 2020

A novel MRGPRX2-targeting antagonistic DNA aptamer inhibits histamine release and prevents mast cell-mediated anaphylaxis.

Eur J Pharmacol 2020 Jul 19;878:173104. Epub 2020 Apr 19.

Department of Pharmacology, Ehime University Graduate School of Medicine, Shitsugawa, Toon, Ehime, Japan.

Anaphylaxis during general anaesthesia is a significant clinical challenge for anaesthesiologists. Approximately 50% of perioperative anaphylaxis cases lack the presence of specific IgE antibodies. Mas-related G-protein coupled receptor X2 (MRGPRX2) in humans and its mouse orthologue Mas-related G-protein coupled receptor B2 (Mrgprb2) are crucial receptors in non-IgE-dependent histamine release. Anaesthetics such as rocuronium and atracurium cause perioperative anaphylaxis by activating histamine release via the Mrgprb2 pathway. We hypothesized that antagonistic DNA aptamers that target MRGPRX2 can prevent perioperative anaphylaxis. Selection of a DNA aptamer that specifically binds MRGPRX2 was achieved by using our modified Systematic Evolution of Ligands by Exponential enrichment (SELEX) approach. Our SELEX process used MRGPRX2-proteoliposomes synthesised by a wheat germ cell-free system as templates. The activity of the selected aptamer to inhibit histamine release from MRGPRX2-activated mast cells and in an anaphylaxis rat model transplanted with this cell line was examined. Our selection process identified aptamer-X35 with the sequence 5'-ATGACCATGACCCTCCACACTGTAGGCACCACGGGTCCCTGGCAGTTAAAAGTACGTTTGTCAGACTGTGGCAGGGAAACA-3'. In silico 2D modelling of aptamer-X35 revealed a structure with a small loop and a long stem. Aptamer-X35 inhibited histamine release from mast cells by 70%. Subcutaneous injection of 30 nmol of aptamer-X35 inhibited the anaphylactic reaction in the rat anaphylaxis model. This study demonstrated that aptamer-X35 selected by the modified SELEX approach reduced histamine release by inhibiting the MRGPRX2 pathway. Overall, our findings establish aptamer-X35 as a potential therapeutic candidate against perioperative anaphylaxis.
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http://dx.doi.org/10.1016/j.ejphar.2020.173104DOI Listing
July 2020

Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord.

Neurochem Int 2020 03 9;134:104672. Epub 2020 Jan 9.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. Electronic address:

Chronic constriction injury of the sciatic nerve is frequently considered as a cause of chronic neuropathic pain. Marked activation of microglia in the posterior horn (PH) has been well established with regard to this pain. However, microglial activation in the anterior horn (AH) is also strongly induced in this process. Therefore, in this study, we compared the differential activation modes of microglia in the AH and PH of the lumbar cord 7 days after chronic constriction injury of the left sciatic nerve in Wistar rats. Microglia in both the ipsilateral AH and PH demonstrated increased immunoreactivity of the microglial markers Iba1 and CD11b. Moreover, abundant CD68 phagosomes were observed in the cytoplasm. Microglia in the AH displayed elongated somata with tightly surrounding motoneurons, whereas cells in the PH displayed a rather ameboid morphology and were attached to myelin sheaths rather than to neurons. Microglia in the AH strongly expressed NG2 chondroitin sulfate proteoglycan. Despite the tight attachment to neurons in the AH, a reduction in synaptic proteins was not evident, suggesting engagement of the activated microglia in synaptic stripping. Myelin basic protein immunoreactivity was observed in the phagosomes of activated microglia in the PH, suggesting the phagocytic removal of myelin. CCI caused both motor deficit and hyperalgesia that were evaluated by applying BBB locomotor rating scale and von Frey test, respectively. Motor defict was the most evident at postoperative day1, and that became less significant thereafter. By contrast, hyperalgesia was not severe at day 1 but it became worse at least by day 7. Collectively, the activation modes of microglia were different between the AH and PH, which may be associated with the difference in the course of motor and sensory symptoms.
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http://dx.doi.org/10.1016/j.neuint.2020.104672DOI Listing
March 2020

B lymphocytopenia and Bregs in a not-to-die murine sepsis model.

Biochem Biophys Res Commun 2020 02 14;523(1):202-207. Epub 2019 Dec 14.

Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan. Electronic address:

Sepsis is a leading cause of mortality in intensive care units due to multi-organ failure caused by dysregulated immune reactions. In this study, kinetic changes in the immune system were analyzed for 72 h in cecal ligation and puncture (CLP)-induced septic mice while preventing animal death by keeping body temperature. Increase of myeloid cells and decrease of B cells in circulation at 6 h after CLP were markedly observed. At the same time point, interleukin (IL)-10 expressing CD5 regulatory B cells (Bregs) appeared. IL-10 and programmed death-ligand 1 (PD-L1) mRNA as well as IL-1β, IL-6 and interferon γ (IFNγ) mRNA was increased in the spleen at 6 h. A gradual decrease in Bcl-2 and abrupt increase of Bim expression in the spleen at the late phase were also found. These results showed that B lymphocytopenia with the appearance of Bregs is the earliest event, likely leading to immunoparalysis in sepsis.
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http://dx.doi.org/10.1016/j.bbrc.2019.12.041DOI Listing
February 2020

Aggravating effects of treadmill exercises during the early-onset period in a rat traumatic brain injury model: When should rehabilitation exercises be initiated?

IBRO Rep 2019 Dec 22;7:82-89. Epub 2019 Oct 22.

Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.

Physical exercise is one of the best interventions for improving traumatic brain injury (TBI) outcomes. However, an argument has been raised regarding the timing at which physical exercise should be initiated. In this study, male Wistar rats were subjected to stab wounding of the right hemisphere to develop a TBI model and were forced to walk once on a treadmill at a 5-m/min pace at 24 h or 48 h after TBI for 10 min. Injured brain tissue was dissected after TBI to evaluate the effects of exercise. Behavioral abnormalities and motor impairment were assessed by various behavioral tests between 2 and 3 weeks after TBI. Exercise did not affect the circulating corticosterone levels and the weight of the adrenal glands. Exercise particularly that at 24 h, worsened the motor impairment of the left forelimbs. Quantitative reverse-transcription polymerase chain reaction showed that exercise at 24 h increased proinflammatory cytokines and chemokines on the third day while suppressing the proinflammatory reactions on the fourth day. Exercise at both time points decreased expression of transforming growth factor (TGF) β1 and its receptor TGFβR1. Exercise at 24 h increased phosphorylation of IκB kinase on the fourth day, which may be correlated with the decreased effects of TGFβ1. Even a low-intensity exercise activity could cause deleterious effects when it is initiated within 48 h after the onset of severe TBI, probably because of the resulting proinflammatory effects. Therefore, rehabilitation exercise programs should be initiated after 48 h of TBI onset.
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http://dx.doi.org/10.1016/j.ibror.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838542PMC
December 2019

Adverse events associated with continuous interscalene block administered using the catheter-over-needle method: a retrospective analysis.

BMC Anesthesiol 2019 10 28;19(1):195. Epub 2019 Oct 28.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon City, Ehime, Japan.

Background: Continuous interscalene block is widely used for pain management in shoulder surgery. However, continuous interscalene block performed using the catheter-through-needle method is reportedly associated with adverse events such as pericatheter leakage of the local anesthetic, phrenic nerve paralysis, and hoarseness. Because we expected that the catheter-over-needle method would reduce these adverse events, we examined cases in which continuous interscalene block was performed using the catheter-over-needle method to determine what adverse events occurred and when.

Methods: We retrospectively reviewed the anesthesia and medical records of adult patients who underwent catheter insertion to receive a continuous interscalene block performed using the catheter-over-needle method at our hospital from July 2015 to July 2017.

Results: During the surveillance period, 122 adult patients underwent catheter insertion to receive a continuous interscalene block administered using the catheter-over-needle method. No case of pericatheter local anesthetic leakage was observed. Adverse events, such as dyspnea, hoarseness, insufficient anesthetic effect, dizziness, cough reflex during drinking, or ptosis, were observed in 42 patients (34.4%; 95% confidence interval 26-42.7). Most of the adverse events occurred on postoperative day 2. The median time between surgery and the onset of adverse events was 28.5 h.

Conclusions: The catheter-over-needle method may prevent the pericatheter leakage of the local anesthetic. However, adverse events occurred in more than one-third of the patients. During continuous interscalene block, patients must be carefully observed for adverse events, especially on postoperative day 2.

Trial Registration: This study was registered at the UMIN Clinical Trials Registry on August 13th, 2019 ( UMIN000037673 ).
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http://dx.doi.org/10.1186/s12871-019-0873-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816201PMC
October 2019

Prediction of the service life of surgical instruments from the surgical instrument management system log using radio frequency identification.

BMC Health Serv Res 2019 Oct 15;19(1):695. Epub 2019 Oct 15.

Department of Medical Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Toon city, Ehime, 791-0295, Japan.

Background: Bar code- or radio frequency identification (RFID)-based medical instrument management systems have gradually been introduced in the field of surgical medicine for the individual management and identification of instruments. We hypothesized that individual management of instruments using RFID tags can provide previously unavailable information, particularly the precise service life of an instrument. Such information can be used to prevent medical accidents caused by surgical instrument failure. This study aimed to predict the precise service life of instruments by analyzing the data available in instrument management systems.

Methods: We evaluated the repair history of instruments and the usage count until failure and then analyzed the data by the following three methods: the distribution of the instrument usage count was determined, an instrument failure probability model was generated through logistic regression analysis, and survival analysis was performed to predict instrument failure.

Results: The usage count followed a normal distribution. Analysis showed that instruments were not used uniformly during surgery. In addition, the Kaplan-Meier curves plotted for five types of instruments showed significant differences in the cumulative survival rate of different instruments.

Conclusions: The usage history of instruments obtained with RFID tags or bar codes can be used to predict the probability of instrument failure. This prediction is significant for determining the service life of an instrument. Implementation of the developed model in instrument management systems can help prevent accidents due to instrument failure. Knowledge of the instrument service life will also help in developing a purchase plan for instruments to minimize wastage.
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http://dx.doi.org/10.1186/s12913-019-4540-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794753PMC
October 2019

Hemolytic reaction in the washed salvaged blood of a patient with paroxysmal nocturnal hemoglobinuria.

BMC Anesthesiol 2019 05 22;19(1):83. Epub 2019 May 22.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.

Background: In patients with paroxysmal nocturnal hemoglobinuria (PNH), the membrane-attack complex (MAC) formed on red blood cells (RBCs) causes hemolysis due to the patient's own activated complement system by an infection, inflammation, or surgical stress. The efficacy of transfusion therapy for patients with PNH has been documented, but no studies have focused on the perioperative use of salvaged autologous blood in patients with PNH.

Case Presentation: A 71-year-old man underwent total hip replacement surgery. An autologous blood salvage device was put in place due to the large bleeding volume and the existence of an irregular antibody. The potassium concentration in the transfer bag of salvaged RBCs after the wash process was high at 6.2 mmol/L, although the washing generally removes > 90% of the potassium from the blood. This may have been caused by continued hemolysis even after the wash process. Once activated, the complement in patients with PNH forms the MAC on the RBCs, and the hemolytic reaction may not be stopped even with RBC washing.

Conclusions: Packed RBCs, instead of salvaged autologous RBCs, should be used for transfusions in patients with PNH. The use of salvaged autologous RBCs in patients with PNH should be limited to critical situations, such as massive bleeding. Physicians should note that the hemolytic reaction may be present inside the transfer bag even after the wash process.
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http://dx.doi.org/10.1186/s12871-019-0752-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530164PMC
May 2019

Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions.

Tissue Barriers 2019 31;7(1):1593775. Epub 2019 Mar 31.

c Department of Molecular and Cellular Physiology, Graduate School of Medicine , Ehime University , Toon , Ehime , Japan.

Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase ≥40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31/CD45 endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis.
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http://dx.doi.org/10.1080/21688370.2019.1593775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592591PMC
August 2020

Impella 5.0 Mechanical Assist Device Catheter-Induced Severe Hemolysis Due to Giant Swinging Motion - New Concern in Impella Usage.

Circ J 2019 09 21;83(10):2080. Epub 2019 Mar 21.

Department of Cardiology, Pulmonology, Hypertension, and Nephrology, Ehime University Graduate School of Medicine.

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http://dx.doi.org/10.1253/circj.CJ-18-1039DOI Listing
September 2019

Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage.

Brain Res 2019 05 19;1710:22-32. Epub 2018 Dec 19.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. Electronic address:

Carbon monoxide (CO) causes not only acute fatal poisoning but also may cause a delayed neurologic syndrome called delayed encephalopathy (DE), which occasionally occurs after an interval of several days to several weeks post-exposure. However, the mechanisms of DE have not been fully elucidated. This study aimed to clarify the pathophysiology of CO-induced DE and its distinctive features compared with hypoxemic hypoxia. Rats were randomly assigned to three groups; the air group, the CO group (exposed to CO), and the low O group (exposed to low concentration of O). Impairment of memory function was observed only in the CO group. The hippocampus tissues were collected and analyzed for assessment of CO-induced changes and microglial reaction. Demyelination was observed only in the CO group and it was more severe and persisted longer than that observed in the low O group. Moreover, in the CO group, decreased in microglial cell numbers were observed using flow cytometry, and microglia with detached branches were observed were observed using immunohistochemistry. Conversely, microglial cells with shortened branches and enlarged somata were observed in the low O group. Furthermore, mRNAs encoding several neurotrophic factors expressed by microglia were decreased in the CO group but were increased in the low O group. Thus, CO-induced DE displayed distinctive pathological features from those of simple hypoxic insults: prolonged demyelination accompanying a significant decrease in microglial cells. Decreased neurotrophic factor expression by microglial cells may be one of the causes of CO-induced DE.
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http://dx.doi.org/10.1016/j.brainres.2018.12.027DOI Listing
May 2019

Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea.

Glia 2018 10 8;66(10):2158-2173. Epub 2018 Sep 8.

Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.

Microglia and blood-borne macrophages in injured or diseased brains are difficult to distinguish because they share many common characteristics. However, the identification of microglia-specific markers and the use of flow cytometry have recently made it easy to discriminate these types of cells. In this study, we analyzed the features of blood-borne macrophages, and activated and resting microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Generation of mitochondrial reactive oxygen species (ROS) was markedly observed in granulocytes and macrophages, but not in activated or resting microglia. Dihydroethidium staining supported microglia not being the major source of ROS in TBI lesions. Furthermore, macrophages expressed NADPH oxidase 2, interleukin-1β (IL-1β), and CD68 at higher levels than microglia. In contrast, microglia expressed transforming growth factor β1 (TGFβ1), interleukin-6 (IL-6), and tumor necrosis factor α at higher levels than macrophages. A hypnotic, bromovalerylurea (BU), which has anti-inflammatory effects, reduced both glycolysis and mitochondrial oxygen consumption. BU administration inhibited chemokine CCL2 expression, accumulation of monocytes/macrophages, 8-OHdG generation, mitochondrial ROS generation, and proinflammatory cytokine expression, and markedly ameliorated the outcome of the TBI model. Yet, BU did not inhibit microglial activation or expression of TGFβ1 and insulin-like growth factor 1 (IGF-1). These results indicate that macrophages are the major aggravating cell type in TBI lesions, in particular during the acute phase. Activated microglia may even play favorable roles. Reduction of cellular energy metabolism in macrophages and suppression of CCL2 expression in injured tissue may lead to amelioration of TBI.
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http://dx.doi.org/10.1002/glia.23469DOI Listing
October 2018

Lower limb perfusion during robotic-assisted laparoscopic radical prostatectomy evaluated by near-infrared spectroscopy: an observational prospective study.

BMC Anesthesiol 2018 08 18;18(1):114. Epub 2018 Aug 18.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon City, Ehime, Japan.

Background: Decreased perfusion in the lower extremities is one of the several adverse effects of placing patients in a lithotomy or Trendelenburg position during surgery. This study aimed to evaluate the effects of patient positioning in lower limb perfusion patients undergoing robotic-assisted laparoscopic radical prostatectomy (RARP) using near-infrared spectroscopy (NIRS).

Methods: This observation study comprised 30 consenting males with American Society of Anaesthesiologists physical status classes I and II (age range, ≥20 to < 80 years). Regional saturation of oxygen measurements was obtained using an INVOS™ oximeter (Somanetics, Troy, MI, USA). A NIRS sensor was positioned on the surface of the skin at the mid-diaphyseal region of the calf muscles (the gastrocnemius and soleus), over the posterior compartment, in the right lower leg. Regional saturation of oxygen (rSO) was sampled during the following time points: before and 5 min after induction of anaesthesia (T0,T1); 5 min after establishment of pneumoperitoneum in a 0° lithotomy position (T2); 5 min after a 25° Trendelenburg position (T3); 30, 60, 90 and 120 min after pneumoperitoneum in a Trendelenburg position (T4, T5, T6 and T7, respectively); after desufflation in a supine position (T8); and after tracheal extubation (T9).

Results: Lower limb perfusion evaluated by NIRS was increased after induction of anaesthesia and maintained during steep Trendelenburg positions in RARP patients with no risk for lower limb compartment syndrome (LLCS) (T0:65 ± 7.2%, T1:69 ± 6.1%, T2:70±:6.1%, T3:68 ± 6.7%, T4:66 ± 7.5%, T5:67 ± 6.9%, T6:68 ± 7.2%, T8:73 ± 7.2%, T9:71 ± 7.9%, respectively).

Conclusions: Lower limb perfusion evaluated by NIRS was maintained during the RARP procedure. Correct patient positioning and careful assessment of risk factors such as vascular morbidity could be important for the prevention of LLCS during RARP.
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http://dx.doi.org/10.1186/s12871-018-0567-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098825PMC
August 2018

Real-time ultrasound-guided infraorbital nerve block to treat trigeminal neuralgia using a high concentration of tetracaine dissolved in bupivacaine.

Scand J Pain 2015 Jan 1;6(1):51-54. Epub 2015 Jan 1.

Ehime University Graduate School of Medicine, Department of Anesthesia and Perioperative Medicine, Ehime Japan.

Background Trigeminal neuralgia is a neuropathic disorder characterized by episodes of intense pain in the face. Drug therapy is the first choice of treatment. However, in cases where drug therapy are contraindicated due to side effects, patients can get pain relief from lengthy neurosurgical procedures. Alternatively, a peripheral trigeminal nerve block can be easily performed in an outpatient setting. Therefore it is a useful treatment option for the acute paroxysmal period of TN in patients who cannot use drug therapy. We performed real-time ultrasound guidance for infraorbital nerve blocks in TN patients using a high concentration of tetracaine dissolved in bupivacaine. In this report, we examine the efficacy of our methods. Patients As approved by the Institutional Review Board, the medical records in our hospital were queried retrospectively. Six patients with TN at the V2 area matched the study criteria. All patients could not continue drug therapy with carbamazepine due to side effects and they received an ultrasound-guided infraorbital nerve block with a high concentration of tetracaine dissolved in bupivacaine. Methods The patient was placed in the supine position and the patient's face was sterilized and draped. An ultrasound system with a 6-13 MHz linear probe was used with a sterile cover. The probe was inserted into the horizontal plane of the cheek just beside the nose and was slid in the cranial direction to find the dimple of the infraorbital foramen. The 25G 25 mm needle was inserted from the caudal side just across from the probe using an out-of-plane approach. To lead the needle tip to the foramen, needle direction was corrected with real-time ultrasound guidance. After the test block with lidocaine (2%, 0.5 ml), a solution of tetracaine (20 mg) dissolved in bupivacaine (0.5%, 0.5 ml) was injected. During each injection, the spread of the agent around the nerve was confirmed using ultrasound images. Results Ten blocks were performed for six patients. Immediately after the procedure, all 10 blocks produced analgesia and relieved the pain. In the three blocks, pain was experienced in a new trigger point outside of the infraorbital nerve region (around the back teeth) within a week after the block and pain were relieved using other treatment. Two patients developed small hematomas in the cheek but they disappeared in a week. All patients did not complain about other side effects including paraesthesia, hyperpathia, dysaesthesia, or double vision. Hypoaesthesia to touch and pain in the infraorbital region were observed in all blocks after 2 weeks. Conclusions We performed real-time ultrasound-guided infraorbital nerve block for TN with a high concentration of tetracaine dissolved in bupivacaine. Our method achieved a high success rate and there were only minor and transient side effects. Implications Real-time ultrasound-guided infraorbital nerve block is one of the useful options to treat the acute paroxysmal period of TN at the infraorbital nerve area. Ultrasound-guided injections may become the standard practice for injecting peripheral trigeminal nerves. Using this high concentration of tetracaine as a neurolytic agent is effective and appears to have only minor side effects.
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http://dx.doi.org/10.1016/j.sjpain.2014.10.003DOI Listing
January 2015

Effect of dexmedetomidine on intraocular pressure in patients undergoing robot-assisted laparoscopic radical prostatectomy under total intravenous anesthesia: A randomized, double blinded placebo controlled clinical trial.

J Clin Anesth 2018 Sep 5;49:30-35. Epub 2018 Jun 5.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon City, Ehime 790-0295, Japan. Electronic address:

Study Objective: To study the effects of intraoperative dexmedetomidine on the intraocular pressure (IOP) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALRP) under propofol-remifentanil anesthesia.

Design: Double-blind, randomized controlled trial.

Setting: Operating room.

Patients: Forty consenting male patients aged ≥20 to <80 years with American Society of Anesthesiologists physical status classes I and II.

Interventions: The patients were randomly assigned to either dexmedetomidine (DEX) (n = 20) or control (n = 20) group. Anesthesia was induced and maintained using propofol, remifentanil, and rocuronium. In the dexmedetomidine group, dexmedetomidine was administered at 0.4 μg/kg/h immediately after anesthesia induction until the end of the surgery, whereas normal saline was administered as placebo in the control group.

Measurements: IOP was measured using a rebound tonometer. Time points of measuring IOP were as follows: T1: before anesthesia induction, T2: 5 min after intubation, T3: 60 min after placing patient in the Trendelenburg position, T4: 120 min after placing patient in the Trendelenburg position, T5: 180 min after placing patient in the Trendelenburg position, T6: 5 min after placing patient in a horizontal position, T7: 5 min after extubation, and T8: 30 min after extubation.

Main Results: A linear mixed model analysis demonstrated a significant intergroup difference in IOP over time and during pneumoperitoneum in the steep Trendelenburg position. IOP at T5 was significantly lower in the dexmedetomidine group than in the control group even after post-hoc analysis in the steep Trendelenburg position periods with Bonferroni correction.

Conclusions: Dexmedetomidine combined with propofol decreases IOP in the steep Trendelenburg position during RALRP.
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http://dx.doi.org/10.1016/j.jclinane.2018.06.006DOI Listing
September 2018

Development of a postoperative occlusive thrombus at the site of an implanted inferior vena cava filter: A case report.

Medicine (Baltimore) 2018 Jan;97(3):e9675

Department of Anesthesia and Perioperative Medicine Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.

Rationale: Although an inferior vena cave (IVC) filter is placed to prevent fatal pulmonary embolism (PE), several complications associated with an IVC filter have been reported. We describe a case with symptomatic PE, of which the origin was an occlusive IVC thrombus that developed from the placement of an IVC filer after a laparoscopy-assisted total gastrectomy (LATG).

Patient Concerns: A 71-year-old man underwent LATG under general anesthesia alone. He had an IVC filter implanted 13 years ago. An intravenous infusion of unfractionated heparin was substituted for the discontinuation of oral warfarin four days before the surgery. The proposed operation was performed and took a total of 404 minutes including the total duration of pneumoperitoneum that took 374 minutes. After the surgery, he experienced severe shivering reactions that required frequent bolus infusions of antihypertensive drugs. On the third postoperative day, he complained of dyspnea after taking a short walk, and subsequently lost consciousness. While he spontaneously recovered without requiring any resuscitation efforts, we performed computed tomography (CT) examination for suspected PE.

Diagnoses: The CT showed that a massive thrombus was occupying the intravenous space from the IVC filter to the left common iliac vein with several embolic defects in the peripheral pulmonary arteries present.

Interventions: An anticoagulant therapy was established with 10 mg of oral apixaban given twice a day for the first four days, followed by a reduction to 5 mg.

Outcomes: On the 17th postoperative day, an ultrasound vascular examination confirmed the complete disappearance of deep venous thrombus (DVT).

Lessons: As an IVC filter itself may be a potential source of DVT, we should carefully manage patients with a previously implanted IVC filter throughout the perioperative period.
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http://dx.doi.org/10.1097/MD.0000000000009675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779783PMC
January 2018

Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a novel Wistar rat metastasis model.

Biochem Biophys Res Commun 2018 02 12;496(2):542-548. Epub 2018 Jan 12.

Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan. Electronic address:

CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The results showed that 100% of rats with C6-L tumors developed lung metastases, while metastases were found in only 44% of rats with C6-S tumors (n = 25). Tumors disappeared in approximately 20% of the C6-S-bearing rats, and these animals evaded death 180 d after transplantation, while all C6-L tumor-bearing rats died after 45 d. Next generation sequencing revealed that C6-S tumors expressed chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry revealed that C6-S tumors contained more dead cells and more CD45 cells, including natural killer cells and CD8 lymphocytes. In particular, multiple subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were more abundant in C6-S than in C6-L tumors. These results suggested that CD200S induced the accumulation of multiple dendritic cell subsets that activated cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells.
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http://dx.doi.org/10.1016/j.bbrc.2018.01.065DOI Listing
February 2018
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