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岡野 光真医学部附属病院 循環器内科助教
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■ 論文- We should consider parathyroid extraglandular bleeding for patients with acute neck pain and swelling. Evaluation of serum calcium and parathyroid hormone levels is crucial for a suspected neck hematoma associated with parathyroid adenoma.2024年09月, Clinical case reports, 12(9) (9), e9383, 英語, 国際誌研究論文（学術雑誌）
- No mechanistic lead is known for establishing AL amyloid deposits in organs. We here report an electron microscopic (EM) analysis in a case of intestinal AL amyloidosis before initiating treatment for amyloidosis. The dense deposits of amyloid fibrils are concentrated around the small blood vessels in the submucosal area of intestinal tissue. Surprisingly, we observed endothelial cells (ECs) of blood vessels containing plenty of endocytotic (pinocytotic) and transcytotic vesicles at the luminal side and above the basement membrane, indicating the one-way active trafficking of either the immunoglobulin (Ig) light chain or preassembled amyloid fibrils from the luminal side of ECs to the extraluminal area of ECs. Immunoelectron microscopy displayed that the immuno-gold signals were observed in the vascular cavity and the subendothelial area of amyloid deposits. However, there is no sign of an Ig light chain in pinocytotic vesicles. Therefore, the intestinal ECs may actively pump out mainly the preassembled amyloid fibrils (not light chains) from the blood stream into the subendothelial area as a physiologic function.2024年01月, Experimental hematology, 129, 104129 - 104129, 英語, 国際誌研究論文（学術雑誌）
- A 38-year-old man with deep vein thrombosis associated with Behçet's disease (BD) was admitted to our hospital due to worsening symptoms despite the initiation of direct oral anticoagulants (DOACs). Administration of oral prednisolone and an intravenous anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody dramatically improved his symptoms. In addition, he was incidentally diagnosed with autosomal dominant polycystic kidney disease, which increases the risk of aortic aneurysms. BD also increases the risk of aortic aneurysms. This case suggests that immunosuppressive treatment is effective in patients with inflammation-related DOAC-refractory venous thrombosis who also suffer from BD.2023年07月, Internal medicine (Tokyo, Japan), 62(13) (13), 2009 - 2012, 英語, 国内誌研究論文（学術雑誌）
- UNLABELLED: Fixed-ratio combination injection therapy (FRC) is a fixed-ratio mixture containing basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) in a single injection for the treatment of patients with type 2 diabetes. The two types of FRC products contain different concentrations and mixing ratios of basal insulin and GLP-1 RA. Both products demonstrated satisfactory blood glucose control throughout the day, with less hypoglycemia and weight gain. However, few studies have examined the differences in the actions of the two formulations. Herein, we present a case of a 71-year-old man with pancreatic diabetes and significantly impaired intrinsic insulin secretion capacity, who demonstrated a marked difference in glycemic control following treatment with two different FRC formulations. Treatment with IDegLira, an FRC product, demonstrated suboptimal glucose control in the patient. However, after a change in therapy to another FRC product, IGlarLixi, his glucose control markedly improved, even with a decrease in the injection dose. This difference could have been due to lixisenatide, a short-acting GLP-1RA contained in IGlarLixi, which exerts a postprandial hypoglycemic effect irrespective of intrinsic insulin secretion capacity. In conclusion, IGlarLixi has the potential to achieve good fasting and postprandial glucose control with a once-daily injection, even in patients with type 2 diabetes who have a reduced intrinsic insulin secretion capacity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-023-00621-5.2023年07月, Diabetology international, 14(3) (3), 294 - 297, 英語, 国内誌
- A 59-year-old man suspected of having myocardial infarction with sinus bradycardia, a decreased blood pressure, and ST-change on an electrocardiogram was referred to our hospital's emergency department. Emergent coronary angiography revealed no significant findings. However, the patient experienced shock and required intensive care. Curiosity rose when his urination volume was not disturbed; we suspected hormonal abnormalities. A hormonal examination and imaging analysis revealed panhypopituitarism caused by a Rathke's cyst. Appropriate hormonal replacement therapy improved his symptoms and led to normalization of his electrocardiogram findings. Acute coronary syndrome (ACS) is a fatal disease; however, clinicians must not discount panhypopituitarism, as it may mimic ACS symptoms.2023年02月, Internal medicine (Tokyo, Japan), 62(4) (4), 559 - 564, 英語, 国内誌研究論文（学術雑誌）
- A 25-year-old Nepalese woman was referred to our hospital because of fever and intermittent abdominal pain with inguinal lymphadenopathy, which had lasted for several months. A liver biopsy of the positron emission tomography-positive lesion led to a diagnosis of hepatic tuberculosis. After the initiation of antituberculosis treatment, her symptoms resolved. However, 11 days after treatment initiation, chest and back pain, high-grade fever, and vomiting appeared and gradually worsened. She developed anemia and her serum ferritin level was elevated. Hemophagocytic syndrome due to the initial deterioration of tuberculosis was suspected and steroid therapy was initiated with the continuation of the antituberculosis drugs. Thereafter, the patient's condition improved remarkably.2022年05月, Cureus, 14(5) (5), e24644, 英語, 国際誌
- Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare clinical entity characterized by "remitting," "seronegative," and "symmetrical" synovitis with pitting edema on the dorsum of the hands and feet. Although rheumatic or malignant diseases are diseases that are known to coexist with RS3PE, other factors such as medication, infection, and vaccination have been reported to be associated with RS3PE. Here, we present a case of RS3PE syndrome that satisfied all four diagnostic criteria of RS3PE (pitting edema in the limbs, acute onset, age ≥ 50 years, and/or rheumatoid factor negativity) after mRNA-1273 SARS-CoV-2 vaccination.2022年05月, Cureus, 14(5) (5), e24952, 英語, 国際誌
- We should consider the complication of bladder rupture for patients with worsened abdominal pain and inability to pass urine following acute cystitis. A CT scan is a useful first-line modality when evaluating for a suspected bladder rupture.2021年06月, Clinical case reports, 9(6) (6), e04312, 英語, 国際誌研究論文（学術雑誌）
- This work established a new murine venous thromboembolism (VTE) model. This model has multiple novel features representing clinical VTE that include the following: 1) deep venous thrombosis (DVT) was formed and extended in the long axis of femoral/saphenous vein; 2) thrombus was formed in a venous valve pocket; 3) deligation of suture-induced spontaneous pulmonary emboli of fibrin-rich DVT; and 4) cardiac motion-free femoral/saphenous vein allowed high-resolution intravital microscopic imaging of fibrin-rich DVT. This new model requires only commercially available epifluorescence microscopy. Therefore, this model has significant potential for better understanding of VTE pathophysiology.2020年04月, JACC. Basic to translational science, 5(4) (4), 344 - 356, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Normal findings of cardiac scintigraphy predict good outcomes. However, a paucity of the data exists for elderly patients 85 years or older. In the present study, we aimed to demonstrate the association between the abnormal findings of cardiac scintigraphy and the risk of all cause death in patients 85 years or older. METHODS: We enrolled 143 consecutive patients 85 years or older with known or suspected coronary artery disease who underwent stress scintigraphy under adenosine or an exercise test and a 99mTechnetium (Tc)-labeled tracer or thallium 201 (201Tl), dual tracer rest scintigraphy using 201Tl and 123I-β-methyl iodophenyl pentadecanoic acid (123I-BMIPP), or 123I-BMIPP single tracer scintigraphy. Ischemia was defined by an induced perfusion abnormality according to a provocation test with recovery at rest or decreased uptake of 123I-BMIPP despite normal perfusion at rest. Infarction was defined by perfusion abnormalities assessed by images at rest on 201Tl or 99mTc-labeled tracer. We defined these findings as abnormal when at least one of these aforementioned characteristics was observed. RESULTS: Patients in the abnormal findings group (N = 62) were more likely to have undergone prior coronary angiography and to have decreased ejection fraction than those in the normal findings group (N = 81). The median follow-up duration was 797 days (interquartile range, 635-1045 days), with follow-up rates of 90% at 1 year and 73% at 2 years. The 2-year mortality rate were significantly higher in the abnormal findings group than in the normal findings group (26.8% vs. 10.9%; p = 0.01). The risk of abnormal findings relative to normal findings remained significant for the mortality (adjusted hazard ratio, 5.99; 95% CI, 1.37-42.8; P = 0.015). CONCLUSION: Abnormal myocardial scintigraphy findings were associated with the increased risk for mortality, even for patients 85 years or older.2019年11月, BMC cardiovascular disorders, 19(1) (1), 246 - 246, 英語, 国際誌研究論文（学術雑誌）
- Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) have an important role in lifestyle-related diseases. To evaluate species differences, we compared LPL and HTGL activities in different animal models of lifestyle-related diseases using the same assay kit. Normal animals (JW rabbits, ICR mice, and SD rats), a hypercholesterolemic animal model (WHHLMI rabbits), and obese animal models (KK-Ay mice and Zucker fatty rats) fed standard chow were used in this study. Plasma was prepared before and after an intravenous injection of heparin sodium under fasting and feeding. LPL and HTGL activities were measured with the LPL/HTGL activity assay kit (Immuno-Biological Laboratories) using an auto-analyzer. Only in mice, high HTGL activity was observed in pre-heparin plasma. In normal animals, LPL and HTGL activities were high in ICR mice and SD rats but low in JW rabbits. Compared to normal animals, LPL activity was high in Zucker fatty rats and WHHLMI rabbits at both fasting and feeding, while LPL activity after feeding was low in KK-Ay mice. HTGL activity was higher in fasted and fed WHHLMI rabbits and fasted Zucker fatty rats, but was lower in fed KK-Ay mice. Gender difference was observed in HTGL activity in SD rats and LPL activity in WHHLMI rabbits but not in ICR mice. In conclusion, this simple assay method was effective for measuring LPL and HTGL activities of experimental animals, and the activities are highly regulated depending on animal species, animal models, feeding/fasting conditions and genders.2019年08月, Experimental animals, 68(3) (3), 267 - 275, 英語, 国内誌研究論文（学術雑誌）
- Rheumatoid vasculitis is a rare etiology for pulmonary hypertension (PH) in patients with connective tissue disease. We encountered a case of acute PH crisis in a case with rheumatoid vasculitis eight months after undergoing adalimumab reduction. Since no repetition of arthralgia occurred after the adalimumab reduction, we decided to not increase the dose of adalimumab. However, hemodynamic collapse thereafter developed and even though steroid pulse therapy was administered, the patient nevertheless died. The autopsy showed clusters of acute and chronic inflammation around the remodeled pulmonary arteries along with micro-thrombi in the vessel lumen. We should consider the possibility of critical worsening of PH as a phenotype of vasculitis related to immunosuppressive therapy reduction.2019年, Internal medicine (Tokyo, Japan), 58(4) (4), 593 - 601, 英語, 国内誌研究論文（学術雑誌）
- SAGE Publications Ltd, 2018年10月, Pulmonary Circulation, 8(4) (4), 英語研究論文（学術雑誌）
- Antiphospholipid syndrome (APS) is a cause of chronic thromboembolic pulmonary hypertension (CTEPH) and it is associated with an increased risk of postoperative neurological complications. We experienced a case of reversible parkinsonism after pulmonary endarterectomy (PEA) and subsequent multiple cerebral infarctions under standard anticoagulation therapy in a patient with CTEPH associated with APS. Strict management using a combination of antiplatelet and anticoagulation therapy should be considered in patients with a high titer of triple antiphospholipid antibodies in the perioperative period. We should be aware of the high risk of postoperative neurologic manifestations in patients with APS.2018年07月, Internal medicine (Tokyo, Japan), 57(14) (14), 2019 - 2023, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND AND AIMS: Aortic valve stenosis (AS) is the most common valvular heart disease and can be life-threatening. The pathogenesis of aortic valve calcification remains largely unknown, primarily due to the lack of an adequate animal model. The high-cholesterol diet-induced AS model in rabbits is one of the established models, but it has the significant limitation of liver dysfunction leading to low survival rates. We hypothesized that a myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbit, an animal model of familial hypercholesterolemia and atherosclerosis, is a useful animal model of AS. METHODS: WHHLMI rabbits, aged 20 months and 30 months (n = 19), and control Japanese White rabbits (n = 4), aged 30 months, were used and evaluated by echocardiography under anesthesia. Pathological evaluation and quantitative analyses by polymerase chain reaction (PCR) were also performed. RESULTS: The lipid profile was similar between 20 months and 30 months. Two rabbits died due to spontaneous myocardial infarction during the study. Thirty-month-old WHHLMI rabbits exhibited significantly smaller aortic valve area (0.22 ± 0.006 cm2vs. 0.12 ± 0.01 cm2, p < 0.05) and higher maximal transvalvular pressure gradient (7.0 ± 0.32 vs. 9.9 ± 0.95 mmHg, p < 0.05) than 20 month-old rabbits. Macroscopic examination of excised aortic valves demonstrated thickened and degenerated valve leaflets at 30 months. Histological evaluation confirmed thickened leaflets with calcified nodules at 30 months. Real-time PCR of resected aortic valve also showed increased expression level of calcification-related molecules including osteopontin, Sox9, Bmp2, RANKL, osteoprotegerin, and Runx2 (p < 0.05 each) in 30-month-old rabbits. CONCLUSIONS: WHHLMI rabbits may be useful models of early-stage AS in vivo.2018年06月, Atherosclerosis, 273, 8 - 14, 英語, 国際誌研究論文（学術雑誌）
- 日本臨床分子医学会, 2018年04月, 日本臨床分子医学会学術総会プログラム・抄録集, 55回, 58 - 58, 日本語新規マウス血栓モデルによる赤血球凝集主体のDVT生体イメージング
- (一社)日本循環器学会, 2018年03月, 日本循環器学会学術集会抄録集 82回, 82回, PJ015 - 1, 英語再構成HDLのphospholipid組成はその抗炎症作用に影響する(Phospholipid Composition of Reconstitute High Density Lipoproteins Affects Their Anti-inflammatory Effects)(英語)
- Clinical efficacy of combination therapy using vasodilators for pulmonary arterial hypertension (PAH) is well established. However, information on its safety are limited. We experienced a case of primary Sjogren's syndrome associated with PAH where the patient developed pulmonary edema immediately after the introduction of upfront triple combination therapy. Although the combination therapy successfully stabilized her pre-shock state, multiple ground glass opacities (GGO) emerged. We aborted the dose escalation of epoprostenol and initiated continuous furosemide infusion and noninvasive positive pressure ventilation (NPPV), but this did not prevent an exacerbation of pulmonary edema. Chest computed tomography showing diffuse alveolar infiltrates without inter-lobular septal thickening suggests the pulmonary edema was unlikely due to cardiogenic pulmonary edema and pulmonary venous occlusive disease. Acute respiratory distress syndrome was also denied from no remarkable inflammatory sign and negative results of drug-induced lymphocyte stimulation tests (DLST). We diagnosed the etiological mechanism as pulmonary vasodilator-induced trans-capillary fluid leakage. Following steroid pulse therapy dramatically improved GGO. We realized that overmuch dose escalation of epoprostenol on the top of dual upfront combination poses the risk of pulmonary edema. Steroid pulse therapy might be effective in cases of vasodilator-induced pulmonary edema in Sjogren's syndrome associated with PAH.2018年, Respiratory medicine case reports, 23, 55 - 59, 英語, 国際誌
- OBJECTIVE: Recent genome-wide association studies newly identified the human KIAA1462 gene as a new locus for coronary artery disease. However, the function of the gene product, named JCAD (junctional protein associated with coronary artery disease), is unknown. Because JCAD is expressed at cell-cell junctions in endothelial cells, we hypothesized and tested whether JCAD regulates angiogenic processes in vitro and in vivo. APPROACH AND RESULTS: Cell culture experiments revealed impaired angiogenic ability (proliferation, migration, and cord formation) by the knockdown of JCAD with siRNA (P<0.05 versus control siRNA). We have generated mice lacking JCAD (mKIAA1462-/-) by gene-targeted deletion of JCAD to address in vivo angiogenic function. mKIAA1462-/- mice did not show morphological differences in development of retinal vasculature. Ex vivo aortic ring model demonstrated impaired neovascularization in aorta from mKIAA1462-/- mice than control wild-type mice (P<0.05). Tumor growth was assessed by monitoring tumor volume after the subcutaneous injection of melanoma, LLC (Lewis lung carcinoma), and E0771 cells into the mice. mKIAA1462-/- mice exhibited significantly smaller tumor volume compared with wild-type mice (P<0.001). Histological assessment of the tumor exhibited less smooth muscle actin-positive neovascularization determined by CD31-positive vascular structure in tumor of mKIAA1462-/- mice than wild-type mice, indicating that knockdown of JCAD inhibited the vascular maturation in pathological angiogenic process. CONCLUSIONS: These in vitro and in vivo studies suggest that JCAD has a redundant functional role in physiological angiogenesis but serves a pivotal role in pathological angiogenic process after birth.2017年09月, Arteriosclerosis, thrombosis, and vascular biology, 37(9) (9), 1667 - 1673, 英語, 国際誌研究論文（学術雑誌）
- 【背景】検査の進歩にもかかわらず，左回旋枝 (LCX) が責任病変の急性冠症候群 (ACS) の診断はむずかしい．【目的】LCX閉塞時の心電図変化の特徴を明らかにするために，LCXの狭窄病変に対するバルーン閉塞中の心電図変化を観察し，逆に心電図変化から灌流域を推定できるか否かを後ろ向きに検討することを目的とした．【方法】当院で2013年4月から2014年2月までに施行したLCXの非閉塞性病変へのPCIを施行中の心電図変化について，冠動脈造影から推定される灌流域と比較し，Cabrera配列を利用して灌流域を推定できるか否かを検討した．【結果】20例のLCXのPCI症例のうち，14例 (70%) でI, aVL誘導の変化，5例 (25%) でII, III, aVF誘導の変化，9例 (45%) でaVR誘導の変化を認めた．6例では心電図変化を認めなかった．バルーン閉塞中に心電図変化を認めた14例のうち11例で，冠動脈造影検査で評価した灌流域を推定でき，陽性的中率0.786 (95%CI: 0.652-0.786) だった．【結論】左回旋枝のバルーン閉塞中は多彩な心電図変化を示し，典型的な側壁誘導だけでなく，下壁誘導やaVR誘導の変化も認めた．Cabrera配列を利用した灌流域の推定が可能であった．特定非営利活動法人 日本冠疾患学会, 2016年, 日本冠疾患学会雑誌, 23(1) (1), 6 - 11, 日本語
- Introduction. The aim of this study was to examine the incidence and risk factors of catheterization-related CI in the contemporary era, using diffusion-weighted magnetic resonance imaging. Methods. We retrospectively analyzed consecutive 84 patients who underwent MRI (magnetic resonance imaging) after 2.81 ± 2.4 days (mean ± SD) of catheterization via aortic arch. We categorized the patients by the presence or absence of acute CI determined by diffusion-weighted MRI and analyzed the incidence and predictors. Results. Of 84 patients that underwent MRI after catheterization, acute CI was determined in 27 (32.1%) patients. In univariate analysis, dyslipidemia, age, coronary artery disease, antiplatelet agents, number of catheters used, urgent settings, and interventional procedures were significantly different. Multivariate analysis revealed dyslipidemia (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.41-16.03; p = 0.01), higher age (OR, 1.09; 95% CI, 1.007-1.19; p = 0.03), and the number of catheters used (OR, 2.21; 95% CI, 1.21-4.36; p = 0.01) as independent predictors of the incidence of catheterization-related acute CI. Conclusions. Dyslipidemia, higher age, and number of catheters used were independent predictors for acute CI after catheterization. These findings imply that managing dyslipidemia and comprehensive planning to minimize the numbers of catheters are important.2016年, BioMed research international, 2016, 6052125 - 6052125, 英語, 国際誌研究論文（学術雑誌）
- 2014年11月, BMJ case reports, 2014, 英語, 国際誌研究論文（学術雑誌）
- 46歳男性, 既往に前壁OMI. 3枝病変による不安定狭心症に対し, CABG施行. 術後6日後よりNarrow QRS PVCを契機に, QRS軸の変化する多形性VTが出現した. 各種治療無効でVT stormとなり, 術後13日目にtriggered PVCを指標に, アブレーションを施行. 低電位領域を左室内apex～midの前側壁に認めた. 同部位辺縁で, アブレーションカテーテル (Abl) 電極にて, 近位から遠位への興奮順序 (sequence) を伴うPurkinje電位記録部位においてSpike-QRS 56msの潜時を伴うPerfect mapを得た. 同部位で, 多形性VTの自然発作が記録され, Poly VT時, Abl電極でPurkinje電位を認め, 体表面QRSに64ms先行していた. 多形性VT中, Purkinje電位間隔の変動が心室電位間隔の変動に先行し, Abl電極のsequence変化とQRS軸の変化が同期して出現した. 同部位の通電開始で多形性VTが出現し, 通電中に停止した. 多形性VTの維持機序に障害Purkinje網でのリエントリ関与が示唆されたので, 報告する.Japan Heart Foundation, 2014年, 心臓, 46(3) (3), S3_212 - S3_218, 日本語
- 2023年, 日本高血圧学会総会プログラム・抄録集(CD-ROM), 45thSacubitril/Valsartan(ARNI)投与前後で耐糖能評価を行った1例
- 2019年05月, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 39, 英語Establishment of Femoral Vein Ligation Model: a New DVT Imaging Model研究発表ペーパー・要旨（国際会議）
- 福田記念医療技術振興財団, 2018年12月, 福田記念医療技術振興財団情報, (31) (31), 67 - 70, 日本語国際交流 実績報告 Novel murine deep venous thrombosis (DVT) model enables real-time in vivo imaging of clinically relevant DVT formation
- 2018年11月06日, CIRCULATION, 138, 英語Establishment of Novel Deep Venous Thrombosis Model Suitable for In Vivo Imaging.研究発表ペーパー・要旨（国際会議）
- 第90回日本循環器学会学術集会, 2026年03月Venous Thrombosis in a Patient with Pseudo-Cushing Syndrome: a Case Report
- 第88回日本循環器学会学術集会, 2024年03月Successful Treatment of Toxic Multinodular Goiter with Atrial Fibrillation and Acute Heart Failure: a Case Report
- 第34回日本老年医学会近畿地方会, 2023年11月症候性の高Ca血症を伴う副甲状腺腺腫に対して、内科的な全身管理後の手術で良好な経過を辿った超高齢の一例
- 第6回日本腫瘍循環器学会学術集会, 2023年09月PET検査と肺動脈カテーテル生検が診断に有用だった子宮肉腫による肺腫瘍塞栓の一例
- 第8回日本肺高血圧・肺循環学会学術集会, 2023年06月CTEPH患者のDVTパターン解析
- 第120回日本内科学会総会, 2023年04月腹部感染症に伴う上腸間膜静脈血栓症の症例検討
- 第86回日本循環器学会学術集会, 2022年03月, 英語Deep Vein Thrombosis Patterns in Chronic Thromboembolic Pulmonary Hypertension Patientsポスター発表
- 第118回日本内科学会総会・講演会, 2021年04月門脈血栓症に対する抗凝固薬の使用経験
- 第83回 日本循環器学会学術集会, 2019年03月, 横浜Novel Deep Venous Thrombosis Model Enabled Visualization of Thrombus Formation and Organization Process in vivo.
- American Heart Association Scientific Sessions 2018., 2018年11月, 英語, シカゴEstablishment of Novel Murine Deep Venous Thrombosis Model Suitable for in vivo Imaging口頭発表（一般）