論文 - 魏 峻洸
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【徹底ガイドDICのすべて 2022-'23】病態生理と病理 病理組織
盛口 清香, 魏 峻洸
救急・集中治療 34 ( 2 ) 584 - 587 2022年7月
記述言語:日本語 掲載種別:研究論文(学術雑誌) 出版者・発行元:(株)総合医学社
<ここがポイント!>▼播種性血管内凝固症候群(DIC)は、種々の基礎疾患によって全身の凝固線溶系が亢進した状態で、凝固系・線溶系のどちらが優位かによって、全身性に多発微小血栓が形成されることによる多臓器障害や、出血傾向をきたす病態である。▼DICの病態生理は、基礎疾患に応じて多彩で、組織所見にも多様性がある。ときに、全身の毛細血管に微小血栓が形成される。▼微小血栓は、主にフィブリンから構成され、血小板が介在する。白血球が混在する場合もある。▼剖検例の検討では、血栓形成の頻度は、主要臓器に高い傾向にある。(著者抄録)
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Tomimori K., Kodama Y., Tanaka H., Yamashita A., Gi T., Asada Y., Doi K., Katsuragi S., Sato Y.
Virchows Archiv 480 ( 6 ) 1181 - 1187 2022年6月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Virchows Archiv
Transient abnormal myelopoiesis (TAM), also known as transient myeloproliferative disorder or transient leukemia, is a self-regressing neoplasia that afflicts infants with trisomy 21. A recent review article documented “myeloid cell thrombus (MCT)” and “fetal vascular malperfusion (FVM)” in placentas with TAM, although the characteristic TAM placental findings have not been clarified. Here, we compared the clinical and pathological placental findings between trisomy 21 patients with or without TAM. In 13 cases of trisomy 21, we identified six placentas with TAM and seven placentas without TAM. The six placentas with TAM included two stillborn cases. Microscopically, MCT was noted in all the cases, and a high incidence of FVM (50%) was observed in TAM cases. Immunohistochemically, MCT was found to be a platelet-rich thrombus. The placentas were grouped according to the presence or absence of TAM and subsequently compared. Clinically, the incidences of abnormal fetal heart rate pattern and fetal or neonatal death were significantly higher in TAM cases. Pathologically, placenta in TAM cases weighted more than those in cases without TAM, and the incidence of MCT was significantly higher in placentas with TAM. Moreover, the incidence of FVM was higher in placentas with TAM, but this difference was not statistically significant. We propose that MCT is a diagnostic feature of placentas with TAM and may be associated with poor fetal outcomes.
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Multiple asymptomatic coronary plaque ruptures and fissures in acute myocardial infarction 査読あり 国際誌
Toshihiro Gi, Shun Nishino, Atsushi Yamashita, Nozomi Watanabe, Yoshisato Shibata, Yujiro Asada
Pathology International 72 ( 6 ) 355 - 357 2022年6月
担当区分:筆頭著者 記述言語:英語 掲載種別:症例報告
DOI: 10.1111/pin.13229
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魏 峻洸, 山下 篤, 浅田 祐士郎
医学のあゆみ 279 ( 11 ) 1084 - 1089 2021年12月
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Pericardial effusion in the course of Fabry disease cardiomyopathy: a case report. 査読あり
Tsuruda T, Higashi Y, Gi T, Nakao S
European heart journal. Case reports 5 ( 10 ) ytab407 2021年10月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:European Heart Journal - Case Reports
Background: Fabry disease (FD) is an X-chromosome-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. Case summary: A 51-year-old Japanese woman with a previous diagnosis of FD presented with pericardial effusion. The exudative pericardial fluid contained globotriaosylsphingosine. Left ventricular hypertrophy progressed despite regular administration of agalsidase alfa every 2 weeks over a 7-year period, with increases in plasma levels of globotriaosylsphingosine and interleukin (IL)-18. In addition, the IL-6 level in the pericardial fluid was markedly higher than that in plasma. Discussion: This case suggests that elevated IL-6 and IL-18 levels in pericardial fluid and plasma indicate the severity of FD cardiomyopathy.
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Intracellular glutamine level determines vascular smooth muscle cell-derived thrombogenicity 査読あり 国際誌
Koyama S., Yamashita A., Matsuura Y., Saito Y., Maekawa K., Gi T., Kitamura K., Asada Y.
Atherosclerosis 328 62 - 73 2021年7月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Atherosclerosis
Background and aims: The everolimus-eluting stent (EES), one of the effective stents for in-stent restenosis (ISR), has a lower incidence of stent thrombosis; however, the underlying mechanism remains unknown. This study aimed to identify the effects of everolimus on vascular metabolism and thrombogenicity and examine their mechanistic link. Methods: EESs and bare-metal stents were implanted in rabbit iliac arteries with smooth muscle cell (SMC)-rich neointima induced by endothelial denudation. Four weeks after stent implantation, the stented arteries were examined for histological analysis and metabolomics. Additionally, everolimus effects in coronary artery SMCs metabolism, tissue factor (TF) expression, and procoagulant activity were assessed in vitro. Results: EES-implanted arteries showed decreased neointima formation, less SMCs infiltration, and reduced TF expression. Concomitantly, they were metabolically characterized by increased levels of metabolites in amino acids, such as glutamine. Similarly, everolimus increased intracellular glutamine levels, decreased TF expression, and reduced procoagulant activity in SMCs in vitro. On the contrary, exogenous glutamine administration also increased intracellular glutamine level, decreased TF expression, and reduced procoagulant activity despite enhanced mammalian target of rapamycin (mTOR) activity. Conclusions: Intracellular glutamine level is likely to determine vascular SMC-related thrombogenicity regardless of mTOR pathway activity. Therefore, increased intracellular glutamine level might contribute partially to the beneficial effect of EES use on stent thrombosis.
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Ogawa S, Kawakami H, Suzuki S, Kuroki D, Uchiyama N, Hatada H, Gi T, Sato Y
Internal medicine (Tokyo, Japan) 60 ( 17 ) 2783 - 2791 2021年3月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:一般社団法人 日本内科学会
Although cases of gastrointestinal toxicity of pembrolizumab have been reported, cases of acute immune-mediated colitis accompanied with metachronous esophageal disorders (esophagitis and ulcer) are rare. We herein report a case of acute colitis and metachronous esophageal ulcers due to an immune-related adverse event following concomitant pembrolizumab chemotherapy for lung adenocarcinoma. To our knowledge, there have so far been no reports of cases in which both acute immune-mediated colitis and metachronous esophageal ulcers developed. We therefore report the details of this case along with a review of the pertinent literature.
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腹部大動脈周囲リンパ節に再発した子宮頸癌が下大静脈に癌塞栓を形成した1例 査読あり
冨森 馨予, 大西 淳仁, 大澤 綾子, 圓崎 夏美, 吉本 望, 福島 和子, 川越 靖之, 中村 栄作, 中村 都英, 魏 峻洸, 佐藤 勇一郎, 鮫島 浩
宮崎県医師会医学会誌 45 ( 1 ) 39 - 43 2021年3月
記述言語:日本語 掲載種別:研究論文(学術雑誌)
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Glioblastoma mimicking metastatic small cell carcinoma: A case report with ultrastructural findings 査読あり 国際誌
Maekawa K., Tokumitsu T., Noguchi H., Nakamura E., Gi T., Horinouchi S., Yamashita S., Takeshima H., Asada Y., Sato Y.
Diagnostic Cytopathology 49 ( 8 ) E291 - E296 2021年2月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Diagnostic Cytopathology
It is often straightforward to distinguish glioblastoma (GBM) from metastatic carcinoma by cytology; however, small cell variants of GBM or GBM with primitive neuronal component (GBMPNC) can mimic metastatic small cell carcinoma (SCC). Herein, we report a case of GBMPNC mimicking metastatic SCC and present cytological and ultrastructural findings. A 65-year-old man with memory disturbance was hospitalized. Magnetic resonance imaging revealed the presence of a 6 cm sized tumor in the right anterior temporal lobe. Intraoperative cytology slides indicated that the tumor consisted of small-sized cells with scant cytoplasm showing high cellularity. The initial intraoperative diagnosis was metastatic SCC; however, any primary visceral tumor was not detected clinically. Immunohistochemical and ultrastructural studies of postoperative histological sections revealed that the lesion was GBMPNC. This case shows that some GBMs may have the potential to closely mimic metastatic SCC, which expands the differential diagnosis and emphasizes the importance of clinical correlation.
DOI: 10.1002/dc.24715
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Gi T, Yamashita A, Aman M, Kuwahara A, Asada Y, Kawagoe Y, Onishi J, Sameshima H, Sato Y
Pathology international 71 ( 4 ) 261 - 266 2021年2月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Pathology International
Ovarian cancer is a known risk factor of venous thromboembolism (VTE). Thrombogenic factor expression and lymphocytic infiltrate have been reported in endometriosis and ovarian cancers. We reviewed 30 cases of ovarian carcinomas (high grade serous carcinoma, 10; endometrioid carcinoma, 10; clear cell carcinoma (CCC), 10) and 16 endometriotic lesions. We immunohistochemically investigated the expressions of tissue factor (TF), podoplanin, P-selectin, and number of CD4 and CD8 positive lymphocytes in cancer tissue and endometriotic lesions, along with their relationship with VTE. The expression of TF was higher in CCC. The TF expression and the number of CD8 positive cells were higher in cancer tissues with VTE than in those without VTE. The podoplanin or P-selectin expression did not differ among histological types or between cases with and without VTE. Our results demonstrated a high TF expression and intraepithelial CD8 cells in CCC, which were associated with VTE. The results suggest that infiltrating lymphocytes may affect TF expression that, in turn, influences VTE.
DOI: 10.1111/pin.13074
その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/pin.13074
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Tsuruda T., Yoshikawa N., Kai M., Yamaguchi M., Toida R., Kodama T., Kajihara K., Kawabata T., Nakamura T., Sakata K., Hatakeyama K., Gi T., Asada Y., Tono T., Kitamura K., Ikeda R.
Internal Medicine 60 ( 3 ) 423 - 429 2021年2月
記述言語:日本語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Internal Medicine
We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.
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Setoguchi K., Yanagi S., Gi T., Tsubouchi H., Uto K., Shigekusa T., Matsumoto N., Sato Y., Nakazato M.
American Journal of Case Reports 22 ( 1 ) e932452 2021年
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:American Journal of Case Reports
Background: Rhabdoid tumor (RT) of the lung is a rare and aggressive malignancy. The origin of and the mutation responsible for RT are entirely unknown. The distinction between RT associated with subtypes of lung cancer and SMARCA4-deficient thoracic sarcomas is also unknown. Three pulmonary subsolid nodules in the right S6, left S6, and left S8 were identified in a 78-year-old Japanese woman. At 3 and 9 months later, a chest CT showed unchanged sizes, but at 15 months the development of a 37-mm mass in the right S6 was observed. The patient’s systemic condition deteriorated rapidly, and she died 1 month later. An autopsy revealed that the mass consisted of 90% RT and 10% lung adenocarcinoma. There were another 2 adenocarcinoma lesions in the left lung. KRAS mutation analyses revealed the same KRAS mutation (G12D) in the adenocarcinoma and RT components in the identical mass and metastatic RT, indicating that all of these components had the same clonality. A different KRAS mutation in each of the 3 adenocarcino-ma lesions was detected (right S6: G12D, left S6: A59G, left S8: G12C), indicating that the multiple adenocar-cinoma lesions were truly multifocal lung adenocarcinoma. The adenocarcinoma and RT components retained SMARCA4 expression. This is the first evidence of RT originating from multifocal lung adenocarcinoma. KRAS mutation is thought to be responsible for the RT’s emergence via the epithelial-mesenchymal transition. Patients with multiple sub-solid nodules should be followed closely; aggressive surgical intervention should be considered given concerns about the evolution of this aggressive malignancy.
DOI: 10.12659/AJCR.932452
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High Signal Intensity on Diffusion-Weighted Images Reflects Acute Phase of Deep Vein Thrombus. 査読あり
Gi T, Kuroiwa Y, Yamashita A, Mizutani Y, Asanuma T, Miyati T, Maekawa K, Aman M, Imamura T, Asada Y
Thrombosis and haemostasis 2020年8月
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Signal Change of Jugular Vein Thrombus on Diffusion-Weighted Magnetic Resonance Imaging 査読あり
Kuga Naoya, Asada Yujiro, Imamura Takuroh, Kuroiwa Yasuyoshi, Sakamoto Takamichi, Yamashita Atsushi, Gi Toshihiro, Doi Shogo, Kinoshita Tomoki, Tanaka Takashi, Kihara Yasushi
Circulation Reports 2 ( 8 ) 455 - 456 2020年
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:一般社団法人 日本循環器学会
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Congenital Abdominal Aortic Aneurysm in a Four Year Old Girl 査読あり 国際誌
Higuchi K., Furukawa K., Nakamura E., Imamura H., Gi T., Nakamura K.
EJVES Vascular Forum 48 12 - 18 2020年
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:EJVES Vascular Forum
© 2020 The Author(s) Introduction: Abdominal aortic aneurysm (AAA) in neonates, infants, and children is uncommon, usually occurring as a result of infections, connective tissue disorders, vasculitis, or iatrogenic trauma. A case of idiopathic congenital AAA, an extremely rare disease of unknown origin, is described. Report: In March 2018, a 40 mm hypoechoic mass adjacent to the left kidney was detected incidentally by abdominal ultrasound for investigation of hypercalciuria in a four year old girl. Contrast enhanced computed tomography (CT) revealed an infrarenal fusiform AAA measuring 39 mm in maximum diameter, a 15 mm left renal artery aneurysm, a 14 mm right hypogastric artery aneurysm, and a 12 mm left hypogastric artery aneurysm. Cerebral magnetic resonance imaging revealed multiple intracranial aneurysms between 8 and 15 mm in diameter. Considering the size of the AAA and risk of rupture, surgical repair was planned. In May 2018, the congenital AAA was successfully repaired with a 10 mm Dacron aorto-aortic tube graft. Increases in the size of the left renal artery aneurysm and a left middle meningeal artery aneurysm were detected 12 and 14 months post-operatively, respectively. Coil embolisations were performed. An intracranial dural arteriovenous fistula (AVF) was discovered incidentally by cerebral angiography for treatment of the left middle meningeal artery aneurysm. Transarterial embolisation for AVF was also performed. At the 21 month post-operative follow up, the patient is doing well, and the untreated aneurysms have not grown. Conclusion: Long term outcomes after surgical repair for congenital AAA are unclear. Moreover, growth of residual aneurysms was detected post-operatively, so follow up with frequent multimodality imaging for multiple aneurysms is necessary.
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Yamashita A., Nishihira K., Gi T., Maekawa K., Hatakeyama K., Horiuchi S., Wada K., Shibata Y., Asada Y.
Thrombosis and Haemostasis 121 ( 2 ) 234 - 241 2020年
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Thrombosis and Haemostasis
© 2020 Georg Thieme Verlag KG Stuttgart New York. Arterial thrombus formation is thought to be initiated by platelet adhesion to the subendothelial matrix, but ruptured atherosclerotic plaques are characterized by substantial reduction of matrix proteins compared with stable plaques. Intraplaque erythrocytes and/or fibrin have been reported in high-risk coronary plaques. The aims of the current study were to identify factors that provide scaffolds for platelets at the sites of ruptured coronary plaques and investigate depositions of iron and bilirubin as hemoglobin catabolites in the ruptured plaques. Histological characteristics of plaque components and the thrombus interface were examined in 73 acute coronary aspirated thrombi. Necrotic debris (95%), macrophages (95%), and cholesterin clefts (81%) were observed frequently at the ruptured plaque and thrombus interface. A fibrous matrix (47%), calcification (32%), and extracellular deoxyribonucleic acid (15%) were identified as small foci. Tissue factor was localized in the necrotic core and macrophages. Fibrin and von Willebrand factor were consistently deposited within the plaques and beneath platelet aggregations. The citrullinated histone H3-immunopositive area accounted for only 0.5% of the plaque area. Bilirubin and iron depositions were detected in approximately 20% of the plaques in addition to biliverdin reductase and ferritin expression in macrophages. Fibrin and von Willebrand factor rather than matrix proteins and neutrophil extracellular traps may be major adhesive molecules at the sites of ruptured plaques. Iron and bilirubin deposits may be markers for rupture-prone plaques.
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Nishino S., Watanabe N., Gi T., Kuriyama N., Shibata Y., Asada Y.
Circulation: Cardiovascular Imaging 13 ( 12 ) e011396 2020年
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Circulation: Cardiovascular Imaging
© 2020 Georg Thieme Verlag. All rights reserved. Background: Recent animal studies have suggested that mitral valve (MV) leaflet remodeling can occur even without significant tethering force and that the postinfarct biological reaction would contribute to the histopathologic changes of the leaflet. We serially evaluated the MV remodeling in patients with anterior and inferior acute myocardial infarction (MI), by using 2-And 3-dimensional transthoracic echocardiography. Additional histopathologic examinations were performed to assess the leaflet pathology. Methods: Sixty consecutive first-onset acute MI (anterior MI, n=30; inferior MI, n=30) patients who underwent successful primary percutaneous coronary intervention were examined (1) before primary percutaneous coronary intervention, (2) at 6-month follow-up, and (3) at follow-up 1 year or later after onset. MV complex geometry including MV leaflet area and thickness was analyzed using dedicated software. Additional histopathologic study compared 18 valves harvested during surgery for ischemic mitral regurgitation (MR). Results: MV area and thickness incrementally increased during the follow-up period. MV leaflet area significantly increased (anterior MI: 5.59 [5.28-5.98] to 6.54 [6.20-7.26] cm2/m2, P<0.001; inferior MI: 5.60 [4.76-6.08] to 6.32 [5.90-6.90] cm2/m2, P<0.001), and leaflet thickness also increased (anterior MI: 1.09 [0.92-1.24] to 1.45 [1.28-1.60] mm/m2, P<0.001; inferior MI: 1.15 [1.03-1.25] to 1.44 [1.27-1.59] mm/m2, P<0.001); data represent onset versus ≥1 year. Larger annuls, larger tenting, and a reduced leaflet area/annular ratio with smaller coaptation index were observed in patients with persistent ischemic MR compared with those without significant ischemic MR. Histopathologic examinations revealed that MV thickness was significantly greater in chronic ischemic MR compared with acute ischemic MR (1432.6±490.5 versus 628.7±278.7 μm; P=0.001), with increased smooth muscle cells and fibrotic materials. Conclusions: MV leaflet remodeling progressed both in area and thickness after MI. This is the first clinical study to record the longitudinal course of MV leaflet remodeling by serial echocardiography.
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Kuroiwa Y., Uchida A., Yamashita A., Miyati T., Maekawa K., Gi T., Noguchi T., Yasuda S., Imamura T., Asada Y.
Cardiovascular Pathology 40 24 - 31 2019年5月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Cardiovascular Pathology
© 2019 Elsevier Inc. Coronary high-signal-intensity plaques (HIPs) detected by T 1 -weighted magnetic resonance imaging are associated with future cardiovascular events. This study aimed to identify pathological findings reflecting HIPs in coronary arteries obtained from autopsy cases. Formalin-fixed hearts were imaged with noncontrast T 1 -weighted imaging with a 1.5-T magnetic resonance system. We defined HIPs or non-HIPs as a coronary plaque to myocardial signal intensity ratio (PMR) of ≥1.4 or <1.4, respectively. We found HIPs in 4 of 37 (10.8%) hearts and analyzed 7 hearts in detail. The corresponding sections to HIPs (n=11) or non-HIPs (n=25) were histologically and immunohistochemically analyzed. We calculated the T 1 relaxation time of human venous blood in vitro. Plaque and necrotic core areas, and the frequency of intraplaque hemorrhage in HIPs were significantly larger/higher than those in non-HIPs. HIPs were immunopositive for CD68 (11/11), glycophorin A (10/11), and fibrin (11/11). Glycophorin-A-, matrix metalloprotease 9 (MMP9)-, and tissue factor-immunopositive areas were larger in HIPs than in non-HIPs. The PMR was positively correlated with glycophorin-A-, fibrin-, MMP9-, and tissue factor-immunopositive areas. Blood coagulation shortened the T 1 relaxation time of the blood and plasma, and the T 1 relaxation times in coagulated whole blood and erythrocyte-rich blood were significantly shorter than those in plasma. Coronary HIPs may reflect intraplaque hemorrhage and may be a novel marker for plaque instability and thrombogenic potential.
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Maekawa K., Sugita C., Yamashita A., Moriguchi-Goto S., Furukoji E., Sakae T., Gi T., Hirai T., Asada Y.
Thrombosis Research 177 136 - 144 2019年5月
記述言語:英語 掲載種別:研究論文(学術雑誌) 出版者・発行元:Thrombosis Research
© 2019 Elsevier Ltd Background: Thrombolytic therapy is effective in fresh deep vein thrombosis (DVT) although the benefit may fall below the risk of bleeding in non-fresh thrombosis. Markers reflecting fresh DVT have not been established. The present study aims to identify metabolites reflecting fresh venous thrombus and their role in thrombus formation. Methods: Metabolites of rabbit venous blood and jugular venous thrombus 4 h after thrombus induction were analysed using electrophoresis-time of flight mass spectrometry. The effects of the altered metabolites on blood coagulation and platelet aggregation were assessed by using rotation thromboelastometry and platelet aggregometer. Cellular contents and glucose transporter (Glut)-1 expression in aspirated human DVT samples were pathologically analysed. Results: Metabolome analysis identified 226 metabolites (133 cationic and 93 anionic metabolites). Largely altered 18 metabolites (thrombus/blood ratio: >5 or <0.5) included glycolytic metabolites, redox-related metabolites, purine nucleotides and tryptophan metabolites. Among the metabolites with >5-fold increase, lactic acid was most abundant and guanine modestly enhanced whole blood clotting with thromboelastometry. Lactic acid and adenosine monophosphate inhibited collagen-induced platelet aggregation. Human DVTs were rich in erythrocytes expressing Glut-1. The erythrocyte content and Glut-1 expression were negatively correlated with the time after onset of DVT. Conclusions: Glycolysis-, purine-, and redox-related metabolites may reflect fresh erythrocyte-rich venous thrombus, and altered metabolites may affect venous thrombus formation. An increased level of lactate may reflect active glycolysis of thrombus cellular components, predominantly erythrocytes.
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A Case of Malignant Transformation of Epidermoid Cyst with Cerebrospinal Fluid Dissemination 査読あり
Suematsu Y, Takeishi G, Yokogami K, Uehara H, Gi T, Yamashita A, Sato Y, Takeshima H
No Shinkei Geka 46 ( 6 ) 509 - 514 2018年6月