89 results on '"Miyashita, K."'
Search Results
2. Incorporation kinetics of rare earth impurities in Si during molecular beam epitaxy
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Miyashita, K., primary, Houghton, D.C., additional, Shiraki, Y., additional, and Fukatsu, S., additional
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- 1996
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3. Cardiac computed tomography-derived coronary artery volume to myocardial mass in patients with severe coronary artery disease.
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Kageyama S, Taylor CA, Updegrove A, Garg S, Masuda S, Revaiah PC, Kageyama M, Tsai TY, Miyashita K, Tobe A, Tanaka K, De Mey J, La Meir M, Schneider U, Doenst T, Teichgräber U, Saima M, Pompilio G, Andreini D, Pontone G, Puskas JD, Gupta H, Morel MA, Serruys PW, and Onuma Y
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Background: Coronary artery lumen volume (V) to myocardial mass (M) ratio (V/M) can show the mismatch between epicardial coronary arteries and the underlying myocardium., Methods: The V, M and V/M were obtained from the coronary computed tomography angiography (CCTA) of patients in the FAST-TRACK CABG study, the first-in-human trial of coronary artery bypass grafting (CABG) guided solely by CCTA and fractional flow reserve derived from CCTA (FFR
CT ) in patients with complex coronary artery disease (CAD). The correlations between V/M ratios and baseline characteristics were determined and compared with those from the ADVANCE registry, an unselected cohort of historical controls with chronic CAD., Results: The V/M ratio was obtained in 106 of the 114 pre-CABG CCTAs. Mean age was 65.6 years and 87% of them were male. The anatomical SYNTAX score from CCTA was significantly higher than the functional SYNTAX score derived using FFRCT [43.1 (15.2) vs 41.1 (16.5), p < 0.001]. Mean V, M, and V/M were 2204 mm3 , 137 g, and 16.5 mm3 /g, respectively. There were weak negative correlations between V and anatomical and functional SYNTAX scores (Pearson's r = -0.26 and -0.34). V and V/M had a strong correlation (r = 0.82). The V/M ratio in the current study was significantly lower than that in the ADVANCE registry (median 16.1 vs. 24.8 [1st quartile 20.1])., Conclusion: Systematically smaller V/M ratios were found in this population with severe CAD requiring CABG compared to an unselected cohort with chronic CAD. The V/M ratio could provide additional non-invasive assessment of CAD especially when combined with FFRCT ., Competing Interests: Declaration of competing interest Dr Serruys has received consultancy fees from Philips/Volcano, SMT, Novartis, Xeltis, Merillife. Dr Garg receives consulting fee from Biosensors. Dr Puskas reports consulting fees from Medtronic, Atricure, Medistim, Edwards Life Science, and royalty payments from Scanlan. Dr Gupta reports an institutional grant from Siemens Health Solutions. Dr Garg reported consulting fees from Biosensors. Dr Taylor and Dr Rogers are employees of HeatFlow Inc. including salary and equity. Dr Thomsen is an employee of GE HealthCare. Dr Pontone reports grants and consultant fees from GE HealthCare, Bracco, and HeartFlow, Payment honoraria from GE HealthCare and HeartFlow, and payment for expert testimony from GE HealthCare. All other authors have no conflict of interest to declare. All other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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4. Retroperitoneal leiomyosarcoma mimicking an ovarian tumor diagnosed using a negative ovarian pedicle sign.
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Mitsuo K, Kaneko H, Tsukamoto M, Asami Y, Miyazawa A, Miyashita K, Onoda G, Yamashita H, Hatano M, Kamiyama M, and Okuda S
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Retroperitoneal leiomyosarcoma (RPLMS) is rare and usually presents as a large abdominal mass with poor clinical symptoms. Radiological findings of an RPLMS arising in the pelvis of a woman resemble those of adnexal tumors. Herein, we present a case of RPLMS mimicking an adnexal tumor which was differentiated from having an ovarian origin as the right ovarian vein was passing through the tumor but there was no direct vascular connection with the tumor. Therefore, it is important to identify the ovarian vein to distinguish between these tumors., (© 2024 The Authors.)
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- 2024
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5. The Impact of Microvascular Resistance Reserve on the Outcome of Patients With STEMI.
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Tsai TY, Aldujeli A, Haq A, Knokneris A, Briedis K, Hughes D, Unikas R, Renkens M, Revaiah PC, Tobe A, Miyashita K, Sharif F, Garg S, Onuma Y, and Serruys PW
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- Humans, Male, Female, Prospective Studies, Aged, Middle Aged, Treatment Outcome, Time Factors, Risk Factors, Prevalence, Coronary Vessels physiopathology, Coronary Vessels diagnostic imaging, Risk Assessment, ST Elevation Myocardial Infarction physiopathology, ST Elevation Myocardial Infarction therapy, ST Elevation Myocardial Infarction mortality, ST Elevation Myocardial Infarction diagnosis, Microcirculation, Vascular Resistance, Predictive Value of Tests, Coronary Circulation, Percutaneous Coronary Intervention adverse effects, Thermodilution, Coronary Artery Disease physiopathology, Coronary Artery Disease therapy, Coronary Artery Disease mortality, Coronary Artery Disease diagnosis
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Background: Microvascular resistance reserve (MRR) can characterize coronary microvascular dysfunction (CMD); however, its prognostic impact in ST-segment elevation myocardial infarction (STEMI) patients remains undefined., Objectives: This study sought to investigate the prevalence of CMD in STEMI patients and to elucidate the prognostic performance of MRR., Methods: This prospective cohort study enrolled 210 STEMI patients with multivessel disease who underwent successful revascularization and returned at 3 months for coronary physiology assessments with bolus thermodilution. The prevalence of CMD (MRR <3) and the association between MRR and major adverse cardiovascular and cerebrovascular events (MACCEs) at 12 months were investigated., Results: The median age of patients was 65 years, and 59.5% were men. At the 3-month follow-up, 56 patients (27%) had CMD (MRR <3.0). The number of MACCEs at 12 months was higher in patients with vs without CMD (48.2% vs 11.0%; P < 0.001). MRR was independently associated with 12-month MACCEs (HR: 0.45 per unit increase; 95% CI: 0.31-0.67; P < 0.001) and with stroke, heart failure, and poorer recovery in left ventricular systolic function. The areas under the receiver-operating characteristic curves for predicting MACCEs at 12 months with fractional flow reserve, coronary flow reserve (CFR), the index of microvascular resistance (IMR), and MRR were 0.609, 0.762, 0.781, and 0.743, respectively. The prognostic performance of CFR, IMR, and MRR were all comparable., Conclusions: The novel parameter MRR is a prognostic marker of MACCEs in STEMI patients with a comparable performance to CFR and IMR. (Impact of TMAO Serum Levels on Hyperemic IMR in STEMI Patients [TAMIR]; NCT05406297)., Competing Interests: Funding Support and Author Disclosures The study was sponsored by the Lithuanian University of Health Sciences. Dr Aldujeli recently held shares in Pfizer Inc. Dr Unikas is the President of the National Interventional Cardiology Association of Lithuania. Dr Tobe has received research grants from the Fukuda Foundation for Medical Technology. Dr Miyashita has received research grants from OrbusNeich Medical K.K. outside the submitted work. Dr Sharif has received grants from SFI Infrastructure 17/RI/5353. Dr Garg has received consulting fees from Biosensors outside the submitted work. Dr Serruys has received consulting fees from SMT, Novartis, Xeltis, Merillife, and Philips outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2024
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6. Frequency of periprocedural myocardial injury and infarction stratified by cardiac troponin I and cardiac troponin T.
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Revaiah PC, Tsai TY, Wang B, Renkens M, Kageyama S, Wlodarczak A, Lemoine J, Mollmann H, Sabate M, Sharif F, Zaman A, Wykrzykowska J, Benit E, Qiang HX, Miyashita K, Tobe A, Muramatsu T, Tanabe K, Ozaki Y, Garg S, McEvoy JW, Neumann FJ, Baumbach A, Smits PC, Stone G, Onuma Y, and Serruys PW
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Background: There are different definitions of periprocedural myocardial infarction (PPMI) both in terms of thresholds for cardiac biomarkers and the ancillary criteria for myocardial ischemia. Cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT) are used interchangeably to diagnose PPMI., Objectives: This study evaluated the frequency of periprocedural myocardial injury and infarction as defined by the Society of Cardiovascular Angiography & Interventions (SCAI), the Academic Research Consortium-2 (ARC-2), and the 4th Universal definition of MI (4UDMI) stratified using cTnT versus cTnI, among patients with chronic coronary syndrome (CCS) and unstable angina., Results: Among 830 patients, PPMI rates according to the SCAI, ARC2 and 4UDMI criteria were 4.34 %, 2.05 %, and 4.94 % respectively, with higher rates seen for all definitions when using cTnI versus cTnT (SCAI: 9.84 % vs. 1.91 %, p < 0.001; ARC 2: 3.15 % vs. 1.56 %, p = 0.136; and 4UDMI 5.91 % vs. 4.51 %, p = 0.391). Minor and major periprocedural myocardial injury was respectively observed in 58.31 % and 27.10 % of patients, with rates of both significantly higher when using cTnI versus cTnT (Minor: 69.29 % vs. 53.47 %, p < 0.001, Major: 49.21 % vs. 17.36 %, p < 0.001)., Conclusions: Among patients with CCS and unstable angina, PPMIs defined by SCAI occurred more frequently when using cTnI as opposed to cTnT, whereas the type of troponin had no impact on the incidence of PPMIs according to the ARC-2 and 4UDMI., Competing Interests: Declaration of competing interest Dr. Ninomiya reports a grant from Abbott Medical Japan outside the submitted work. Dr. Kotoku has received a grant for studying overseas from Fukuda Foundation for Medical Technology. Dr. Serruys reports institutional grants from Sinomedical Sciences Technology, SMT (Sahajanand Medical technologies), Meril Life sciences, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Onuma reports institutional grants from Sinomedical Sciences Technology, SMT (Sahajanand Medical technologies), Meril Life sciences, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Sabate is a consultant for Abbott vascular and iVascular outside the submitted work. Dr. Mollmann is a consultant for Abbott vascular, Boston Scientific, Medtronic and SMT outside the submitted work., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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7. Quantitative coronary computed tomography assessment for differentiating between total occlusions and severe stenoses.
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Masuda S, Revaiah PC, Kageyama S, Tsai TY, Miyashita K, Tobe A, Puskas JD, Teichgräber U, Schneider U, Doenst T, Tanaka K, De Mey J, La Meir M, Mushtaq S, Bartorelli AL, Pompilio G, Garg S, Andreini D, Onuma Y, and Serruys PW
- Abstract
Backgrounds: The impact of quantitative assessment to differentiate total occlusions (TOs) from severe stenoses on coronary computed tomography angiography (CCTA) remains unknown., Objective: This study investigated whether quantitative characteristics assessed on CCTA could help differentiate a TO from a severe stenosis on invasive coronary angiography (ICA)., Methods: This study is a sub-analysis of the FASTTRACK CABG (NCT04142021) in which both CCTA and ICA were routinely performed. Quantitative analysis was performed with semi-automated CCTA plaque-analysis software. Blinded analysts compared TOs on CCTA, defined as a complete lack of contrast opacification within the coronary occlusion, with corresponding ICA., Results: Eighty-four TOs were seen on CCTA in 59 of the 114 patients enrolled in the trial. The concordance in diagnosing a TO between ICA and CCTA was 56.0% (n = 47). Compared to severe stenoses, TOs had a significantly longer lesion length (25.1 ± 23.0 mm vs 9.4 ± 11.2 mm, P < 0.001). The best cut-off value to differentiate a TO from severe stenosis was a lesion length of 5.5 mm (area under the curve 0.77, 95% CI: 0.66-0.87), with a 91.1% sensitivity and 61.1% specificity. Dense calcium percentage atheroma volume (PAV) was significantly higher in TOs compared to severe stenoses (18.7 ± 19.6% vs. 6.6 ± 13.0%, P < 0.001), whilst the opposite was seen for fibro-fatty PAV (31.3 ± 14.2% vs. 19.5 ± 10.5%, P < 0.001). On a multivariable logistic regression analysis, lesion length (>5.5 mm) was the only parameter associated with differentiating a TO from a severe stenosis., Conclusion: In quantitative CCTA analysis, a lesion length >5.5 mm was the only independent predictor differentiating a TO from a severe stenosis., Nct Registration Number: NCT04142021., Competing Interests: Declaration of competing interest Dr. Masuda received a grant from TERUMO corporation outside the submitted work. Dr. Miyashita received research grants from OrbusNeich Medical K.K., outside the submitted work. Dr. Tobe received a grant from the Fukuda foundation for medical technology. Dr. Scot received consultancy fees from Biosensors. Dr. P.W.S. reported consulting fees from SMT, Novartis, Meril Life, Philips, and Xeltis. All other authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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8. Quantification of lipoprotein lipase in mouse plasma with a sandwich enzyme-linked immunosorbent assay.
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Kimura T, Miyashita K, Fukamachi I, Fukamachi K, Ogura K, Yokoyama E, Tsunekawa K, Nagasawa T, Ploug M, Yang Y, Song W, Young SG, Beigneux AP, Nakajima K, and Murakami M
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- Animals, Mice, Rats, Receptors, Lipoprotein metabolism, Receptors, Lipoprotein genetics, Mice, Knockout, Lipoprotein Lipase metabolism, Lipoprotein Lipase blood, Enzyme-Linked Immunosorbent Assay methods, Antibodies, Monoclonal immunology
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To support in vivo and in vitro studies of intravascular triglyceride metabolism in mice, we created rat monoclonal antibodies (mAbs) against mouse LPL. Two mAbs, mAbs 23A1 and 31A5, were used to develop a sandwich ELISA for mouse LPL. The detection of mouse LPL by the ELISA was linear in concentrations ranging from 0.31 ng/ml to 20 ng/ml. The sensitivity of the ELISA made it possible to quantify LPL in serum and in both pre-heparin and post-heparin plasma samples (including in grossly lipemic samples). LPL mass and activity levels in the post-heparin plasma were lower in Gpihbp1
-/- mice than in wild-type mice. In both groups of mice, LPL mass and activity levels were positively correlated. Our mAb-based sandwich ELISA for mouse LPL will be useful for any investigator who uses mouse models to study LPL-mediated intravascular lipolysis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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9. Editorial: Are inflammatory biomarkers following bioresorbable scaffold or drug-eluting stent implantation directly linked to outcomes?
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Serruys PW, Miyashita K, Garg S, and Onuma Y
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- Humans, Absorbable Implants, Everolimus, Biomarkers, Drug-Eluting Stents, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease surgery
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- 2024
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10. Nationwide survey of adult patients with pulmonary alveolar proteinosis using the National Database of designated intractable diseases of Japan.
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Miyashita K, Hozumi H, Inoue Y, Suzuki T, and Suda T
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- Humans, Adult, Male, Middle Aged, Female, Japan epidemiology, Lung, Bronchoalveolar Lavage, Oxygen, Pulmonary Alveolar Proteinosis epidemiology, Pulmonary Alveolar Proteinosis therapy, Autoimmune Diseases therapy
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Background: Autoimmune pulmonary alveolar proteinosis (APAP) and congenital/hereditary PAP were labeled intractable diseases in Japan in 2015. Since then, patients registered in the National Database of Designated Incurable Diseases (NDDID) who met certain requirements became eligible for medical subsidies. Epidemiological studies using recent data are needed for the development of management protocols for patients with PAP., Methods: We conducted the first nationwide study describing the epidemiology and characteristics of PAP using data for patients registered in the Japanese NDDID between 2015 and 2020. We focused on patient demographics, diagnosis, disease severity score (DSS), symptoms, test results, and treatment., Results: We identified 110 patients with PAP, among whom 96.4% had APAP/idiopathic PAP (IPAP). The median age was 58 years, with a slight male predominance. Most patients had a DSS ≥3 (64.5%) and reported symptoms (e.g., dyspnea on exertion). High-resolution computed tomography typically revealed ground glass opacity and crazy paving appearances. Pulmonary function was relatively preserved, except for carbon monoxide diffusing capacity. Only 27.4% of patients underwent therapeutic whole-lung lavage and/or bronchoalveolar lavage, while 25% required long-term oxygen therapy. Serum Krebs von den Lungen-6, surfactant protein D, and lactate dehydrogenase levels significantly and positively correlated with the DSS., Conclusions: Most patients registered in the NDDID have APAP/IPAP with a DSS ≥3, and about one-quarter require long-term oxygen therapy and infrequent lavages. Our results provide important details of the current prevalence and clinical practice related to APAP/IPAP with a DSS ≥3 in Japan., Competing Interests: Conflict of Interest K.M. has no conflict of interest. H.H. has no conflict of interest. Y.I. received honoraria for lecture fees and for serving as a steering committee board member from Boehringer Ingelheim (none of which are related to this manuscript). T. Suzuki. belongs to endowed departments sponsored by Nippon Boehringer Ingelheim Co., Ltd., and AstraZeneca K.K. T. Suda. has no conflict of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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11. Development of hypertriglyceridemia due to GPIHBP1 autoantibodies prior to clinical diagnosis of systemic lupus erythematosus in a 14-year-old girl.
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Kunitsu T, Harada-Shiba M, Sato T, Nonomura K, Kimura T, Miyashita K, Nakajima K, and Murakami M
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- Adolescent, Autoantibodies, Female, Humans, Hypertriglyceridemia diagnosis, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic diagnosis, Receptors, Lipoprotein
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- 2022
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12. Home-Based Exercise Program Ameliorates Renal Function Decline in Patients With CKD Stage 4.
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Adachi K, Uchiyama K, Muraoka K, Nakayama T, Yasuda M, Miyashita K, Tokuyama H, Wakino S, and Itoh H
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- 2022
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13. Significance of Brain Imaging for Staging in Patients With Clinical Stage T1-2 N0 Non-Small-Cell Lung Cancer on Positron Emission Tomography/Computed Tomography.
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Saito G, Kono M, Koyanagi Y, Miyashita K, Tsutsumi A, Kobayashi T, Miki Y, Hashimoto D, Nakamura T, Nozue M, and Nakamura H
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- Aged, Aged, 80 and over, Brain Neoplasms diagnostic imaging, Female, Humans, Male, Middle Aged, Neoplasm Staging methods, Retrospective Studies, Thoracic Neoplasms diagnostic imaging, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology, Neuroimaging, Positron Emission Tomography Computed Tomography
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Background: Routine positron emission tomography/computed tomography (PET/CT) has been recommended even for clinical stage I non-small-cell lung cancer (NSCLC). In spite of the progress in the screening procedure, and revisions to TNM classification, there is no evidence to support brain imaging screening of patients assessed with the current staging protocol including PET/CT., Materials and Methods: We retrospectively investigated the frequency of extrathoracic metastasis in 466 consecutive patients with clinical stage T1-2 N0 NSCLC with the complete staging assessment comprised of thin-section CT, PET/CT, and brain contrast-enhanced magnetic resonance imaging between 2008 and 2016. All patients were reclassified according to the eighth edition of the tumor, node, and metastasis (TNM) classification., Results: Among all patients, 70% of the tumors were pure solid and 30% had part-solid ground-glass opacity on thin-section CT, and 388 (83%) and 78 (17%) were classified into clinical stages T1 and T2, respectively. Eight patients (1.7%) had extrathoracic metastasis, including 3 (0.6%) with brain metastasis, and all showed pure-solid tumors. The frequency of extrathoracic and brain metastasis was 1.0% and 0.5% in 388 T1 patients, and 5.0% and 3.0% in 78 T2 patients. Although brain metastases were detected in 2 of 7 patients (29%) with PET/CT detectable extrathoracic metastases and 1 of 459 patients (0.2%) without PET/CT detectable extrathoracic metastasis, there were no neurologically asymptomatic brain metastases in patients with early-stage NSCLC confirmed by PET/CT., Conclusion: Routine screening of brain imaging is unnecessary in patients with early-stage NSCLC, assessed with the current staging protocol including PET/CT., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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14. Prognostic significance of bronchoalveolar lavage cellular analysis in patients with acute exacerbation of interstitial lung disease.
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Kono M, Miyashita K, Hirama R, Oshima Y, Takeda K, Mochizuka Y, Tsutsumi A, Miwa H, Miki Y, Hashimoto D, Suda T, and Nakamura H
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- Adrenal Cortex Hormones administration & dosage, Aged, Disease Progression, Female, Humans, Idiopathic Pulmonary Fibrosis drug therapy, Idiopathic Pulmonary Fibrosis mortality, Lung Diseases, Interstitial drug therapy, Lung Diseases, Interstitial mortality, Male, Middle Aged, Predictive Value of Tests, Prognosis, Retrospective Studies, Bronchoalveolar Lavage Fluid cytology, Idiopathic Pulmonary Fibrosis diagnosis, Leukocyte Count, Lung Diseases, Interstitial diagnosis, Lymphocytes, Neutrophils
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Background: Acute exacerbation (AE) of interstitial lung disease (ILD) is an acute respiratory deterioration of unknown etiology, associated with high mortality. Currently, bronchoalveolar lavage (BAL) has been no longer required for the diagnosis of AE-ILD; however, the clinical utility of BAL fluid (BALF) cellular analysis in AE-ILD remains unclear., Methods: A retrospective study of 71 patients who underwent BAL at our institution between 2005 and 2019 and were diagnosed with AE-ILD was conducted. We performed BALF cellular analysis and evaluated its prognostic significance., Results: There were 26 patients with AE of idiopathic pulmonary fibrosis (IPF) and 45 with AE of non-IPF, including idiopathic interstitial pneumonias/non-IPF (n = 22), ILD associated with collagen tissue disease (n = 20) and fibrotic hypersensitivity pneumonia (n = 3). All patients were treated with high-dose corticosteroids, and the 90-day mortality after AE was 31%. Most patients showed a high percentage of lymphocytes and/or neutrophils in BALF regardless of the underlying ILD. There was a significant negative correlation between BALF neutrophils and the PaO
2 /FiO2 ratio, and patients with UIP pattern or diffuse AE pattern on HRCT had a significantly higher percentage of BALF neutrophils than those with other patterns. Multivariate analysis revealed that lower and higher percentage of lymphocytes and neutrophils, respectively, in BALF were independent poor prognostic factors for 90-day survival. BALF lymphocyte and neutrophil count ≥25% and <20%, respectively, predicted favorable survival after AE., Conclusions: Cellular analysis of BALF in AE-ILD is a potential biomarker for predicting prognosis after AE., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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15. Detailed analysis of lipolytic enzymes in a Japanese woman of familial lipoprotein lipase deficiency - Effects of pemafibrate treatment.
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Minamizuka T, Kobayashi J, Tada H, Miyashita K, Koshizaka M, Maezawa Y, Ono H, and Yokote K
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- Acute Disease, Benzoxazoles, Butyrates, Female, Humans, Japan, Lipoprotein Lipase genetics, Liver, Triglycerides, Hyperlipoproteinemia Type I genetics, Pancreatitis
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Background: We present here a 72-y-old Japanese woman with lipoprotein lipase (LPL) deficiency and analyzed her lipolytic enzymes in detail before and after pemafibrate treatment., Methods: She had a serum triglycerides (TG) of 22.6 mmol/l at a medical checkup at the age of 52 y. She was referred to our hospital at the age of 61 y. Her serum lipoprotein lipase (LPL) concentration was extremely low, suggesting the clinical diagnosis of LPL deficiency. She experienced an event of acute pancreatitis at the age of 65 y., Results: Next-generation sequencing analysis revealed a homozygous nonsense mutation in the LPL gene, c.1277G > A (p.Trp409Ter). Her serum TG, LPL and hepatic lipase (HL) concentrations were 15.0 mmol/l, 23 ng/ml and 66 ng/ml, respectively. Fifteen minutes after intravenous heparin injection (30 U/kg), her serum TG, LPL and HL concentrations turned to 14.1 mmol/l, 20 ng/ml and 660 ng/ml, respectively. Eight weeks of pemafibrate treatment (0.2 mg/day) caused a modest reductions in serum TG (15.02 → 13.58 mmol/l) and considerable increases in preheparin HL (66 → 76 ng/ml) and PHP-HL (660 → 1118 ng/ml) concentrations and PHP-HL activities (253 → 369U/l) despite almost no effect on LPL concentrations and activities., Conclusions: These findings suggest that HL may contribute to the reduction of plasma TG in LPL deficiency., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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16. Chylomicronemia from GPIHBP1 autoantibodies.
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Miyashita K, Lutz J, Hudgins LC, Toib D, Ashraf AP, Song W, Murakami M, Nakajima K, Ploug M, Fong LG, Young SG, and Beigneux AP
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- Humans, Autoantibodies immunology, Hypertriglyceridemia immunology, Receptors, Lipoprotein immunology
- Abstract
Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody-based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia., Competing Interests: Conflict of interest—K,N. holds stock in Immuno-Biological Laboratories (IBL) and serves as a consultant for Skylight and Sysmex. All other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Miyashita et al.)
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- 2020
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17. Endodermal Cyst with a Non-enhancing Nodule in the Quadrigeminal Cistern Developed in an Octogenarian.
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Miyashita K, Oikawa N, Kobayashi M, Aida Y, Kitabayashi T, Shimizu Y, and Tohma Y
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- Aged, 80 and over, Central Nervous System Cysts complications, Central Nervous System Cysts pathology, Central Nervous System Cysts surgery, Gait Disorders, Neurologic etiology, Gait Disorders, Neurologic physiopathology, Humans, Hydrocephalus diagnostic imaging, Hydrocephalus etiology, Hydrocephalus physiopathology, Magnetic Resonance Imaging, Male, Subarachnoid Space surgery, Urinary Incontinence etiology, Urinary Incontinence physiopathology, Central Nervous System Cysts diagnostic imaging, Endoderm pathology, Subarachnoid Space diagnostic imaging
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Background: Intracranial endodermal cysts are congenital lesions that generally develop in the cerebellopontine angle and ventral brainstem of the posterior fossa, whereas endodermal cysts in the quadrigeminal cistern are very rare. We report a rare case of an endodermal cyst in the quadrigeminal cistern with a non-enhancing nodule that developed in patient over 80 years of age., Case Description: An 85-year-old man presented to our hospital with progressing gait disturbance and urinary incontinence. Preoperative images showed a cystic mass lesion with a nodule in the quadrigeminal cistern and hydrocephalus. There was no enhanced portion in the lesion, and the intensity of the cyst on magnetic resonance imaging revealed a high protein concentration. Subtotal resection was performed due to the adhesion of the cyst to the brainstem. It was diagnosed as an endodermal cyst. The postoperative course was uneventful, and hydrocephalus improved., Conclusions: This is a rare case of an intracranial endodermal cyst in terms of location and age of onset compared with previous reports. This case demonstrates that endodermal cysts should be considered as a differential diagnosis for lesions in the quadrigeminal cistern with high protein concentration in the cyst and nodule representing chronic inflammation, regardless of enhancing effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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18. In Reply to the Letter to the Editor Regarding "Recurrent Spinal Intramedullary Arachnoid Cyst: Case Report and Literature Review".
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Miyashita K and Ichinose T
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- 2020
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19. Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice.
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Takatani N, Kono Y, Beppu F, Okamatsu-Ogura Y, Yamano Y, Miyashita K, and Hosokawa M
- Subjects
- Alanine Transaminase blood, Amino Acids, Animals, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Aspartate Aminotransferases blood, Biomarkers metabolism, Cell Line, Choline, Diet, High-Fat, Disease Models, Animal, Gene Expression Regulation drug effects, Hepatic Stellate Cells drug effects, Hepatic Stellate Cells metabolism, Inflammation blood, Inflammation complications, Inflammation genetics, Lipid Metabolism drug effects, Liver drug effects, Liver injuries, Liver Cirrhosis blood, Liver Cirrhosis complications, Liver Cirrhosis genetics, Male, Metabolome drug effects, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Xanthophylls chemistry, Xanthophylls pharmacology, Inflammation pathology, Liver pathology, Liver Cirrhosis drug therapy, Non-alcoholic Fatty Liver Disease drug therapy, Oxidative Stress drug effects, Xanthophylls therapeutic use
- Abstract
Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte injury, excessive oxidative stress, and chronic inflammation in fatty liver, and can progress to more severe liver diseases, such as cirrhosis and hepatocellular carcinoma. However, currently there are no effective therapies for NASH. Marine carotenoid, fucoxanthin (Fx), abundant in brown seaweeds, has variable biological properties, such as anti-cancer, anti-inflammatory, anti-oxidative and anti-obesity. However, the effect of Fx on the development of NASH has not been explored. We investigated the protective effects of Fx in diet-induced NASH model mice fed choline-deficient L-amino acid-defined high fat diet (CDAHFD). Fx administration significantly attenuated liver weight gain and hepatic fat accumulation, resulting in the alleviation of hepatic injury. Furthermore, the Fx-fed mice, not only exhibited reduced hepatic lipid oxidation, but also decreased mRNA expression levels of inflammation and infiltration-related genes compared to that of the CDAHFD-fed mice. Moreover, fucoxanthinol and amarouciaxanthin A, two Fx metabolites exerted anti-inflammatory effects in the liver via inhibiting the chemokine production in hepatocytes. In case of fibrosis, one of the features of advanced NASH, the expression of fibrogenic factors including activated-hepatic stellate cell marker was significantly decreased in the liver of Fx-fed mice. Thus, the present study elucidated that dietary Fx not only inhibited hepatic oxidative stress and inflammation but also prevented early phase of fibrosis in the diet-induced NASH model mice., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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20. Efficacy and Safety of the Modified EPOCH Regimen (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study.
- Author
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Tsukamoto Y, Kiyasu J, Choi I, Kozuru M, Uike N, Utsunomiya H, Hirata A, Fujioka E, Ohno H, Nakashima E, Nakashima Y, Miyashita K, Tachikawa Y, Narazaki T, Tsuda M, Haji S, Takamatsu A, Tanaka E, Goto T, Takatsuki H, Oyama M, Muta H, Yagi Y, Ikeda M, Matsushima T, Yufu Y, and Suehiro Y
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cyclophosphamide pharmacology, Cyclophosphamide therapeutic use, Doxorubicin pharmacology, Doxorubicin therapeutic use, Etoposide pharmacology, Etoposide therapeutic use, Female, Humans, Leukemia-Lymphoma, Adult T-Cell mortality, Leukemia-Lymphoma, Adult T-Cell pathology, Male, Middle Aged, Prednisone pharmacology, Prednisone therapeutic use, Progression-Free Survival, Retrospective Studies, Vincristine pharmacology, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia-Lymphoma, Adult T-Cell drug therapy
- Abstract
Background: We retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen., Patients and Methods: Patients received up to 6 mEPOCH cycles. Etoposide (50 mg/m
2 /day), doxorubicin (10 mg/m2 /day), and vincristine (0.4 mg/m2 /day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m2 /day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert's formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6., Results: In 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation., Conclusion: The mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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21. Nutraceutical characteristics of the brown seaweed carotenoid fucoxanthin.
- Author
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Miyashita K, Beppu F, Hosokawa M, Liu X, and Wang S
- Subjects
- Adipose Tissue, White drug effects, Adipose Tissue, White metabolism, Animals, Anti-Obesity Agents chemistry, Anti-Obesity Agents metabolism, Antioxidants chemistry, Antioxidants metabolism, Drug Discovery, Free Radicals metabolism, Gene Expression Regulation drug effects, Humans, Hypoglycemic Agents chemistry, Hypoglycemic Agents metabolism, Insulin Resistance, Liver metabolism, Molecular Structure, Neuroprotective Agents chemistry, Neuroprotective Agents metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Scavenger metabolism, Singlet Oxygen metabolism, Uncoupling Protein 1 chemistry, Uncoupling Protein 1 metabolism, Xanthophylls adverse effects, beta Carotene analogs & derivatives, beta Carotene chemistry, Dietary Supplements analysis, Seaweed chemistry, Xanthophylls chemistry, Xanthophylls metabolism
- Abstract
Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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22. Recurrent Spinal Intramedullary Arachnoid Cyst: Case Report and Literature Review.
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Ichinose T, Miyashita K, Tanaka S, Oikawa N, Oishi M, Nambu I, Kinoshita M, and Nakada M
- Subjects
- Arachnoid Cysts surgery, Cervical Cord pathology, Child, Preschool, Humans, Male, Recurrence, Reoperation, Spinal Cord Diseases surgery, Arachnoid Cysts pathology, Spinal Cord Diseases pathology
- Abstract
Background: Symptomatic intramedullary arachnoid cysts are rarely observed lesions, particularly in the pediatric age group. Treatment includes cyst fenestration or resection of the cyst wall, and recurrence after surgery has never been reported. We report a rare case of a spinal intramedullary arachnoid cyst, which recurred after cyst fenestration and required reoperation after a certain period., Case Description: A 4-year-old boy presented to our hospital with tetraparesis and bladder and rectum disorder. A cystic intramedullary lesion in the cervical spinal cord was detected in preoperative imaging. An emergency fenestration of cyst was performed, and his symptoms were resolved immediately. One month after the operation, the symptoms and cyst recurred. The symptoms improved in the natural course without reoperation. However, the cyst increased in size and the symptoms recurred after 27 months from the first relapse and the cyst was removed urgently. The diagnosis was an arachnoid cyst. After the reoperation, the cyst has disappeared and not recurred., Conclusions: To the best of our knowledge, this is the first report of recurrence of an intramedullary arachnoid cyst. This case indicates the importance of considering the resection of cyst wall as possible because of the probability of cyst recurrence after fenestration, while careful observation is the option in the short term, especially for children or high-risk cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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23. Effect of Unilateral Carotid Artery Stenting on Cognitive Function in Patients with Severe Bilateral Stenosis.
- Author
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Nakahara M, Misaki K, Tsutsui T, Nakajima R, Yoshikawa A, Miyashita K, Uchiyama N, and Nakada M
- Subjects
- Acetazolamide, Aged, 80 and over, Carbonic Anhydrase Inhibitors, Carotid Stenosis complications, Carotid Stenosis physiopathology, Carotid Stenosis psychology, Cerebral Angiography, Cerebral Infarction complications, Cerebral Infarction diagnostic imaging, Cerebral Infarction physiopathology, Cerebral Infarction psychology, Dementia complications, Dementia psychology, Diffusion Magnetic Resonance Imaging, Humans, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Perfusion Imaging, Severity of Illness Index, Tomography, Emission-Computed, Single-Photon, Carotid Artery, Internal surgery, Carotid Stenosis surgery, Cognition, Dementia physiopathology, Endovascular Procedures methods, Stents
- Abstract
Case Description: An 82-year-old man with dementia, gait disturbance, and a small cerebral infarction owing to severe bilateral carotid artery stenosis was successfully treated with carotid artery stenting (CAS). Preoperative cerebral vascular reactivity was reduced in the bilateral cerebral hemispheres. We performed CAS to treat right internal carotid artery stenosis. Following CAS, cerebral vascular reactivity showed an increase in the bilateral cerebral hemispheres. Memory, fluency, and attention also showed improvement., Conclusions: This case illustrates the potential benefit of single-stage CAS for cognitive function in severe bilateral carotid artery stenosis without hyperperfusion syndrome., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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24. Intermittent chylomicronemia caused by intermittent GPIHBP1 autoantibodies.
- Author
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Ashraf AP, Miyashita K, Nakajima K, Murakami M, Hegele RA, Ploug M, Fong LG, Young SG, and Beigneux AP
- Subjects
- Adolescent, Autoantibodies blood, Female, Humans, Autoantibodies immunology, Hyperlipoproteinemia Type I immunology, Receptors, Lipoprotein immunology
- Abstract
Chylomicronemia caused by a deficiency in lipoprotein lipase (LPL) or GPIHBP1 (the endothelial cell protein that transports LPL to the capillary lumen) is typically diagnosed during childhood and represents a serious, lifelong medical problem. Affected patients have high plasma triglyceride levels (>1500 mg/dL) and a high risk of acute pancreatitis. However, chylomicronemia frequently presents later in life in the absence of an obvious monogenic cause. In these cases, the etiology for the chylomicronemia is presumed to be "multifactorial" (involving diabetes, drugs, alcohol, or polygenic factors), but on a practical level, the underlying cause generally remains a mystery. Here, we describe a 15-year-old female with chylomicronemia caused by GPIHBP1 autoantibodies (which abolish LPL transport to the capillary lumen). Remarkably, chylomicronemia in this patient was intermittent, interspersed between periods when the plasma triglyceride levels were normal. GPIHBP1 autoantibodies were easily detectable during episodes of chylomicronemia but were undetectable during periods of normotriglyceridemia. During the episodes of chylomicronemia (when GPIHBP1 autoantibodies were present), plasma LPL levels were low, consistent with impaired LPL transport into capillaries. During periods of normotriglyceridemia, when GPIHBP1 autoantibodies were absent, plasma LPL levels normalized. Because the chylomicronemia in this patient was accompanied by debilitating episodes of acute pancreatitis, the patient was ultimately treated with immunosuppressive drugs, which resulted in disappearance of GPIHBP1 autoantibodies and normalization of plasma triglyceride levels. GPIHBP1 autoantibodies need to be considered in patients who present with unexplained acquired cases of chylomicronemia., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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25. Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone.
- Author
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Kono M, Nakamura Y, Enomoto N, Saito G, Koyanagi Y, Miyashita K, Tsutsumi A, Kobayashi T, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Miki Y, Hashimoto D, Fujisawa T, Inui N, Suda T, and Nakamura H
- Subjects
- Humans, Prognosis, Idiopathic Pulmonary Fibrosis drug therapy, Idiopathic Pulmonary Fibrosis physiopathology, Pyridones therapeutic use, Vital Capacity
- Abstract
Background: Pirfenidone (PFD), an oral antifibrotic drug, is conditionally recommended for the treatment of idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the prognostic factors in IPF patients treated with PFD and clarify the clinical significance of marginal physiological changes after PFD therapy., Methods: We retrospectively reviewed 96 consecutive IPF patients treated with PFD. The physiological evaluation was performed at 3-6 months after PFD therapy, and the findings were classified into three groups based on the presence of a 5% change in %forced vital capacity (%FVC): improved, stable, and worsened. The clinical characteristics and prognostic outcomes were compared among groups, and the prognostic factors were evaluated by Cox proportional hazards analysis., Results: Of the 96 patients, 25 (26.0%) showed acute exacerbation (AE) and 40 (41.6%) died during the observation period (median, 17 months). Physiological responses could be evaluated in 80 patients and the findings were as follows: improved, 23%; stable, 36%; and worsened, 41%. Time to the first AE and the survival rate were significantly shorter and lower, respectively, in the worsened group than in the improved/stable group (P = 0.002, P < 0.001, respectively). The prognostic analysis revealed that low %FVC at baseline (hazard ratio [HR]: 0.973 [0.950-0.996]), use of supplemental oxygen (HR: 2.180 [1.041-4.622]), and a "worsened" status after PFD therapy (HR: 5.253 [2.541-11.400]) were significantly associated with a poor prognosis., Conclusions: An early marginal decline in FVC may be important for survival outcomes in PFD-treated IPF patients., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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26. Serum concentration of full-length- and carboxy-terminal fragments of endothelial lipase predicts future cardiovascular risks in patients with coronary artery disease.
- Author
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Nagao M, Miyashita K, Mori K, Irino Y, Toh R, Hara T, Hirata KI, Shinohara M, Nakajima K, and Ishida T
- Subjects
- Aged, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, HEK293 Cells, Humans, Kaplan-Meier Estimate, Male, Proportional Hazards Models, Risk Factors, Coronary Artery Disease blood, Coronary Artery Disease enzymology, Lipase blood, Lipase chemistry
- Abstract
Background: Endothelial lipase (EL), a regulator of plasma high-density lipoprotein cholesterol (HDL-C), is secreted as a 68-kDa mature glycoprotein, and then cleaved by proprotein convertases. However, the clinical significance of the circulating EL fragments remains unclear., Objective: The objective of this study was to analyze the impact of serum EL fragments on HDL-C levels and major adverse cardiovascular events (MACE)., Methods: Using novel monoclonal antibodies (RC3A6) against carboxy-terminal EL protein, we have established a new enzyme-linked immunosorbent assay (ELISA) system, which can detect both full-length EL protein (full EL) and carboxy-terminal truncated fragments (total EL) in serum. The previous sandwich ELISA detected only full EL. The full and total EL mass were measured in 556 patients with coronary artery disease. Among them, 272 patients who underwent coronary intervention were monitored for 2 years for MACE., Results: There was a significant correlation between serum full and total EL mass (R = 0.45, P < .0001). However, the total EL mass showed a stronger inverse correlation with serum HDL-cholesterol concentration than the full EL mass (R = -0.17 vs -0.02). Kaplan-Meier analysis documented an association of serum total EL mass and MACE (log-rank P = .037). When an optimal cutoff value was set at 96.23 ng/mL, total EL mass was an independent prognostic factor for MACE in the Cox proportional hazard model (HR; 1.75, 95% CI; 1.10-2.79, P = .018)., Conclusion: Serum total EL mass could be a predictor for MACE in patients with coronary artery disease. This novel ELISA will be useful for further clarifying the impact of EL on HDL metabolism and atherosclerosis., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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27. Clinical significance of lower-lobe interstitial lung disease on high-resolution computed tomography in patients with idiopathic pleuroparenchymal fibroelastosis.
- Author
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Kono M, Fujita Y, Takeda K, Miyashita K, Tsutsumi A, Kobayashi T, Miki Y, Hashimoto D, Enomoto N, Nakamura Y, Suda T, and Nakamura H
- Subjects
- Aged, Aged, 80 and over, Disease Progression, Female, Humans, Idiopathic Interstitial Pneumonias diagnosis, Idiopathic Interstitial Pneumonias pathology, Idiopathic Pulmonary Fibrosis diagnosis, Idiopathic Pulmonary Fibrosis pathology, Lung Diseases, Interstitial pathology, Lung Diseases, Interstitial therapy, Male, Middle Aged, Mucin-1 blood, Prognosis, Residual Volume, Retrospective Studies, Total Lung Capacity physiology, Vital Capacity physiology, Idiopathic Interstitial Pneumonias complications, Idiopathic Pulmonary Fibrosis complications, Lung Diseases, Interstitial diagnostic imaging, Lung Diseases, Interstitial physiopathology, Tomography, X-Ray Computed methods
- Abstract
Background: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare form of idiopathic interstitial pneumonias (IIP) and may have other patterns of interstitial lung disease (ILD) in the lower lobe, such as usual interstitial pneumonia (UIP). However, the clinical significance of lower-lobe ILD in patients with IPPFE is unclear., Methods: A retrospective review of 40 consecutive patients with clinically diagnosed IPPFE in our institution from 2005 to 2016 was conducted. The presence of lower-lobe ILD on high-resolution computed tomography (HRCT) was assessed and classified into UIP or non-UIP pattern according to a modification of diagnostic criteria for idiopathic pulmonary fibrosis. Clinical characteristics and prognostic factors were evaluated., Results: Among the 40 patients with IPPFE, 21 (53%) had lower-lobe ILD, including 13 with UIP pattern and 8 with non-UIP pattern. Patients with IPPFE who had lower-lobe ILD had significantly older age, higher frequency of fine crackles, higher serum KL-6 level, lower residual volume (RV), and lower total lung capacity (TLC) than those without lower-lobe ILD. In addition, those with lower-lobe ILD, especially UIP pattern, had a significantly poorer survival than those without lower-lobe ILD (log-rank test; p = 0.014, p < 0.001, respectively). Multivariate Cox proportional hazards regression analysis revealed that low %forced vital capacity (%FVC) at baseline and coexistence of UIP pattern were significantly associated with poor prognosis in patients with IPPFE., Conclusions: The coexistence of lower-lobe ILD on HRCT, especially the UIP pattern, may predict poor survival in patients with IPPFE., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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28. Bright spot analysis for photodynamic diagnosis of brain tumors using confocal microscopy.
- Author
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Yoneyama T, Watanabe T, Tamai S, Miyashita K, and Nakada M
- Subjects
- Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology, Female, Glioblastoma diagnostic imaging, Glioblastoma pathology, Glioma diagnostic imaging, Glioma pathology, Humans, Male, Aminolevulinic Acid administration & dosage, Brain Neoplasms diagnosis, Glioblastoma diagnosis, Glioma diagnosis, Microscopy, Confocal methods, Photosensitizing Agents administration & dosage
- Abstract
Background: In a previous study of photodynamic tumor diagnosis using 5-aminolevulinic acid (5-ALA), the authors proposed using fluorescence intensity and bright spot analyses under confocal microscopy for the precise discrimination of tumorous brain tissue (such as glioblastoma, GBM) from normal tissue. However, it remains unclear if bright spot analysis can discriminate infiltrating tumor in the boundary zone and whether this method is suitable for GBM with no 5-ALA fluorescence or for other tumor types., Methods: Brain tumor tissue resected from 5-ALA-treated patients was sectioned to evaluate bright spots under confocal microscopy with a 544.5 - 619.5 nm band-pass filter, which eliminated the fluorescence induced by 5-ALA. Border regions and adjacent normal tissues were observed for differences in bright spot distribution. Histopathology was also conducted by hematoxylin and eosin (H&E) staining of serial slices from the same samples to confirm the locations of tumorous, infiltrating, and normal regions. Bright spot areas were then calculated for the same regions evaluated by histopathology. This method was applied for GBM with and without 5-ALA-induced fluorescence as well as for lower-grade gliomas and other brain tumor types., Results: The bright spot area was substantially smaller in the GBM body than in normal brain tissues. Bright spot area was also smaller in infiltrating tumors than in normal tissue at the margin. The same bright spot pattern was observed in tumorous tissues with no 5-ALA-induced fluorescence and in non-GBM tumors. The bright spot fluorescence is suggested to arise from lipofuscin based on emission spectra (mainly within 544.5 - 619.5 nm) and optimum excitation wavelength (about 405 nm)., Conclusions: Bright spot analysis is useful for discriminating infiltrating tumor from bordering normal tissue as an alternative or complement to photodynamic diagnosis with 5-ALA. This method is also potentially useful for tumors with no 5-ALA-derived red fluorescence and other nervous system tumors., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
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29. GPIHBP1 autoantibody syndrome during interferon β1a treatment.
- Author
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Eguchi J, Miyashita K, Fukamachi I, Nakajima K, Murakami M, Kawahara Y, Yamashita T, Ohta Y, Abe K, Nakatsuka A, Mino M, Takase S, Okazaki H, Hegele RA, Ploug M, Hu X, Wada J, Young SG, and Beigneux AP
- Subjects
- Adult, Autoantibodies blood, Autoimmune Diseases etiology, Cells, Cultured, Female, Humans, Hyperlipoproteinemia Type I etiology, Interferon-beta therapeutic use, Multiple Sclerosis complications, Protein Binding, Syndrome, Triglycerides blood, Withholding Treatment, Autoimmune Diseases immunology, Drug-Related Side Effects and Adverse Reactions immunology, Hyperlipoproteinemia Type I immunology, Interferon-beta adverse effects, Multiple Sclerosis therapy, Receptors, Lipoprotein immunology
- Abstract
Background: Autoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen., Objective: A patient with multiple sclerosis developed chylomicronemia during interferon (IFN) β1a therapy. The chylomicronemia resolved when the IFN β1a therapy was discontinued. Here, we sought to determine whether the drug-induced chylomicronemia was caused by GPIHBP1 autoantibodies., Methods: We tested plasma samples collected during and after IFN β1a therapy for GPIHBP1 autoantibodies (by western blotting and with enzyme-linked immunosorbent assays). We also tested whether the patient's plasma blocked the binding of LPL to GPIHBP1 on GPIHBP1-expressing cells., Results: During IFN β1a therapy, the plasma contained GPIHBP1 autoantibodies, and those autoantibodies blocked GPIHBP1's ability to bind LPL. Thus, the chylomicronemia was because of the GPIHBP1 autoantibody syndrome. Consistent with that diagnosis, the plasma levels of GPIHBP1 and LPL were very low. After IFN β1a therapy was stopped, the plasma triglyceride levels returned to normal, and GPIHBP1 autoantibodies were undetectable., Conclusion: The appearance of GPIHBP1 autoantibodies during IFN β1a therapy caused chylomicronemia. The GPIHBP1 autoantibodies disappeared when the IFN β1a therapy was stopped, and the plasma triglyceride levels fell within the normal range., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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30. An ELISA for quantifying GPIHBP1 autoantibodies and making a diagnosis of the GPIHBP1 autoantibody syndrome.
- Author
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Miyashita K, Fukamachi I, Machida T, Nakajima K, Young SG, Murakami M, Beigneux AP, and Nakajima K
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Syndrome, Young Adult, Autoantibodies blood, Enzyme-Linked Immunosorbent Assay, Receptors, Lipoprotein blood
- Abstract
Background: Autoantibodies against GPIHBP1, the endothelial cell transporter for lipoprotein lipase (LPL), cause severe hypertriglyceridemia ("GPIHBP1 autoantibody syndrome"). Affected patients have low serum GPIHBP1 and LPL levels. We report the development of a sensitive and specific ELISA, suitable for routine clinical use, to detect GPIHBP1 autoantibodies in serum and plasma., Methods: Serum and plasma samples were added to wells of an ELISA plate that had been coated with recombinant human GPIHBP1. GPIHBP1 autoantibodies bound to GPIHBP1 were detected with an HRP-labeled antibody against human immunoglobulin. Sensitivity, specificity, and reproducibility of the ELISA was evaluated with plasma or serum samples from patients with the GPIHBP1 autoantibody syndrome., Results: A solid-phase ELISA to detect and quantify GPIHBP1 autoantibodies in human plasma and serum was developed. Spiking recombinant human GPIHBP1 into the samples reduced the ability of the ELISA to detect GPIHBP1 autoantibodies. The ELISA is reproducible and sensitive; it can detect GPIHBP1 autoantibodies in samples diluted by >1000-fold., Conclusion: We have developed a sensitive and specific ELISA for detecting GPIHBP1 autoantibodies in human serum and plasma; this assay will make it possible to rapidly diagnose the GPIHBP1 autoantibody syndrome., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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31. An automated method for measuring lipoprotein lipase and hepatic triglyceride lipase activities in post-heparin plasma.
- Author
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Nakajima K, Machida T, Imamura S, Kawase D, Miyashita K, Fukamachi I, Maeda M, Muraba Y, Koga T, Kobayashi J, Kimura T, Nakajima K, and Murakami M
- Subjects
- Adult, Aged, Colorimetry, Female, Humans, Kinetics, Lipase metabolism, Lipoproteins blood, Male, Middle Aged, Triglycerides blood, Automation, Lipase blood, Lipoproteins metabolism, Liver enzymology, Triglycerides metabolism
- Abstract
Background: Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) play a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides. Quantification of LPL and HTGL activity is useful for diagnosing lipid disorders, but there has been no automated method for measuring these lipase activities., Methods: The automated kinetic colorimetric method was used for assaying LPL and HTGL activity in the post-heparin plasma using the natural long-chain fatty acid 2-diglyceride as a substrate. LPL activity was determined with apoCII and HTGL activity was determined without apoCII with 2 channel of auto-analyzer., Results: The calibration curve for dilution tests of the LPL and HTGL activity assay ranged from 0.0 to 500 U/L. Within-run CV was obtained within a range of 5%. No interference was observed in the testing of specimens containing potentially interfering substances. The measurement range of LPL activity in the post-heparin plasma was 30-153 U/L, while HTGL activity was 135-431 U/L in normal controls., Conclusions: The L PL and HTGL activity assays are applicable to quantitating the LPL and HTGL activity in the post-heparin plasma. This assay is more convenient and faster than radiochemical assay and highly suitable for the detection of lipid disorders., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2018
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32. Overexpression of Lhx2 suppresses proliferation of human T cell acute lymphoblastic leukemia-derived cells, partly by reducing LMO2 protein levels.
- Author
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Miyashita K, Kitajima K, Goyama S, Kitamura T, and Hara T
- Subjects
- Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Neoplastic, Humans, Up-Regulation, Adaptor Proteins, Signal Transducing metabolism, Cell Proliferation, LIM Domain Proteins metabolism, LIM-Homeodomain Proteins metabolism, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma pathology, Proto-Oncogene Proteins metabolism, Transcription Factors metabolism
- Abstract
T cell acute lymphoblastic leukemia (T-ALL) is a malignant cancer with poor prognosis. The transcriptional co-factor LIM domain only 2 (LMO2) and its target gene HHEX are essential for self-renewal of T cell precursors and T-ALL etiology. LMO2 directly associates with LDB1 in a large DNA-containing nuclear complex and controls the transcription of T-ALL-related genes. Recently, we reported that overexpression of the LIM-homeodomain transcription factor, Lhx2, results in liberation of the Lmo2 protein from the Lmo2-Ldb1 complex, followed by ubiquitin proteasome mediated degradation. Here, we found that proliferation of five human T-ALL-derived cell lines, including CCRF-CEM, was significantly suppressed by retroviral overexpression of Lhx2. The majority of Lhx2-transduced CCRF-CEM cells arrested in G
0 phase and subsequently underwent apoptosis. Expression of LMO2 protein as well as HHEX, ERG, HES1 and MYC genes was repressed in CCRF-CEM cells by transduction with Lhx2. Lhx2-mediated growth inhibition was partially rescued by simultaneous overexpression of Lmo2; however, both the C-terminal LIM domain and the homeodomain of Lhx2 were required for its growth-suppressive activity. These data indicate that Lhx2 is capable of blocking proliferation of T-ALL-derived cells by both LMO2-dependent and -independent means. We propose Lhx2 as a new molecular tool for anti-T-ALL drug development., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2018
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33. An enzyme-linked immunosorbent assay for measuring GPIHBP1 levels in human plasma or serum.
- Author
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Miyashita K, Fukamachi I, Nagao M, Ishida T, Kobayashi J, Machida T, Nakajima K, Murakami M, Ploug M, Beigneux AP, Young SG, and Nakajima K
- Subjects
- Aged, Antibodies, Monoclonal immunology, Cardiovascular Diseases pathology, Case-Control Studies, Female, Humans, Male, Metabolic Diseases pathology, Middle Aged, Receptors, Lipoprotein immunology, Triglycerides blood, Enzyme-Linked Immunosorbent Assay, Receptors, Lipoprotein blood
- Abstract
Background: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol (GPI)-anchored protein of capillary endothelial cells, transports lipoprotein lipase to the capillary lumen and is essential for the lipolytic processing of triglyceride-rich lipoproteins., Objective: Because some GPI-anchored proteins have been detected in plasma, we tested whether GPIHBP1 is present in human blood and whether GPIHBP1 deficiency or a history of cardiovascular disease affected GPIHBP1 circulating levels., Methods: We developed 2 monoclonal antibodies against GPIHBP1 and used the antibodies to establish a sandwich enzyme-linked immunosorbent assay (ELISA) to measure GPIHBP1 levels in human blood., Results: The GPIHBP1 ELISA was linear in the 8 to 500 pg/mL range and allowed the quantification of GPIHBP1 in serum and in pre- and post-heparin plasma (including lipemic samples). GPIHBP1 was undetectable in the plasma of subjects with null mutations in GPIHBP1. Serum GPIHBP1 median levels were 849 pg/mL (range: 740-1014) in healthy volunteers (n = 28) and 1087 pg/mL (range: 877-1371) in patients with a history of cardiovascular or metabolic disease (n = 415). There was an extremely small inverse correlation between GPIHBP1 and triglyceride levels (r = 0.109; P < .0275). GPIHBP1 levels tended to be slightly higher in patients who had a major cardiovascular event after revascularization., Conclusion: We developed an ELISA for quantifying GPIHBP1 in human blood. This assay will be useful to identify patients with GPIHBP1 deficiency and patients with GPIHBP1 autoantibodies. The potential of plasma GPIHBP1 as a biomarker for metabolic or cardiovascular disease is yet questionable but needs additional testing., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
34. A new enzyme-linked immunosorbent assay system for human serum hepatic triglyceride lipase.
- Author
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Miyashita K, Nakajima K, Fukamachi I, Muraba Y, Koga T, Shimomura Y, Machida T, Murakami M, and Kobayashi J
- Subjects
- Antibodies, Monoclonal immunology, Antibody Specificity, Humans, Lipase immunology, Blood Chemical Analysis methods, Enzyme-Linked Immunosorbent Assay methods, Lipase blood, Liver enzymology
- Abstract
There is no established method for measuring human hepatic triglyceride (TG) lipase (HTGL) concentration in serum. In this study, we developed new monoclonal Abs (MoAbs) (9A1 mouse MoAb and 141A1 rat MoAb) that react with HTGL both in serum and in postheparin plasma (PHP) and established a novel ELISA system for measuring serum HTGL and PHP-HTGL concentrations. To confirm the specificity of MoAbs, we performed immunoprecipitation-immunoblotting analysis. Both 9A1 mouse MoAb and 141A1 rat MoAb were able to immunoprecipitate not only recombinant HTGL and PHP-HTGL but also serum HTGL, demonstrating that HTGL exists in serum obtained without heparin injection. This method yielded intra- and interassay coefficients of variation of <6% and showed no cross-reactivity with LPL or endothelial lipase. In clinical analysis on 42 male subjects with coronary artery disease, there were strong positive correlations of serum HTGL concentration to PHP-HTGL concentration ( r = 0.727, P < 0.01). Serum HTGL concentrations showed positive correlations to serum TGs ( r = 0.314, P < 0.05) and alanine aminotransferase ( r = 0.406, P < 0.01), and tendencies toward positive correlations to LDL cholesterol, small dense LDL, and γGTP. These results suggest that this new ELISA method for measuring serum HTGL is applicable in daily clinical practice., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
35. GPIHBP1 autoantibodies in a patient with unexplained chylomicronemia.
- Author
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Hu X, Dallinga-Thie GM, Hovingh GK, Chang SY, Sandoval NP, Dang TLP, Fukamachi I, Miyashita K, Nakajima K, Murakami M, Fong LG, Ploug M, Young SG, and Beigneux AP
- Subjects
- Adult, Animals, Cell Line, Humans, Hyperlipoproteinemia Type I complications, Hyperlipoproteinemia Type I genetics, Hypertriglyceridemia complications, Male, Mutation, Autoantibodies blood, Autoantibodies immunology, Hyperlipoproteinemia Type I blood, Hyperlipoproteinemia Type I immunology, Receptors, Lipoprotein immunology
- Abstract
Background: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the interstitial spaces and transports it to the capillary lumen. GPIHBP1 deficiency prevents LPL from reaching the capillary lumen, resulting in low intravascular LPL levels, impaired intravascular triglyceride processing, and severe hypertriglyceridemia (chylomicronemia). A recent study showed that some cases of hypertriglyceridemia are caused by autoantibodies against GPIHBP1 ("GPIHBP1 autoantibody syndrome")., Objective: Our objective was to gain additional insights into the frequency of the GPIHBP1 autoantibody syndrome in patients with unexplained chylomicronemia., Methods: We used enzyme-linked immunosorbent assays to screen for GPIHBP1 autoantibodies in 33 patients with unexplained chylomicronemia and then used Western blots and immunocytochemistry studies to characterize the GPIHBP1 autoantibodies., Results: The plasma of 1 patient, a 36-year-old man with severe hypertriglyceridemia, contained GPIHBP1 autoantibodies. The autoantibodies, which were easily detectable by Western blot, blocked the ability of GPIHBP1 to bind LPL. The plasma levels of LPL mass and activity were low. The patient had no history of autoimmune disease, but his plasma was positive for antinuclear antibodies., Conclusions: One of 33 patients with unexplained chylomicronemia had the GPIHBP1 autoantibody syndrome. Additional studies in large lipid clinics will be helpful for better defining the frequency of this syndrome and for exploring the best strategies for treatment., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
36. Preserving expression of Pdx1 improves β-cell failure in diabetic mice.
- Author
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Yamamoto Y, Miyatsuka T, Sasaki S, Miyashita K, Kubo F, Shimo N, Takebe S, Watada H, Kaneto H, Matsuoka TA, and Shimomura I
- Subjects
- Animals, Diabetes Mellitus, Experimental genetics, Glucose Intolerance genetics, Glucose Transporter Type 2 genetics, Glucose Transporter Type 2 metabolism, Homeodomain Proteins genetics, Insulin genetics, Insulin-Secreting Cells metabolism, Maf Transcription Factors, Large genetics, Maf Transcription Factors, Large metabolism, Mice, Transgenic, Protein Transport, Trans-Activators genetics, Diabetes Mellitus, Experimental pathology, Homeodomain Proteins metabolism, Insulin-Secreting Cells pathology, Trans-Activators metabolism
- Abstract
Pdx1, a β-cell-specific transcription factor, has been shown to play a crucial role in maintaining β-cell function through transactivation of β-cell-related genes. In addition, it has been reported that the expression levels of Pdx1 are compromised under diabetic conditions in human and rodent models. We therefore aimed to clarify the possible beneficial role of Pdx1 against β-cell failure and generated the transgenic mouse that expressed Pdx1 conditionally and specifically in β cells (βPdx1) and crossed these mice with Ins2
Akita diabetic mice. Whereas Pdx1 mRNA levels were reduced in Ins2Akita mice compared with their non-diabetic littermates, the mRNA levels of Pdx1 were significantly recovered in the islets of βPdx1; Ins2Akita mice. The βPdx1; Ins2Akita mice exhibited significantly improved glucose tolerance, compared with control Ins2Akita littermates, accompanied by increased insulin secretion after glucose loading. Furthermore, histological examination demonstrated that βPdx1; Ins2Akita mice had improved localization of SLC2A2 (GLUT2), and quantitative RT-PCR showed the recovered expression of Mafa and Gck mRNAs in the islets of βPdx1; Ins2Akita mice. These findings suggest that the sustained expression of Pdx1 improves β-cell failure in Ins2Akita mice, at least partially through the preserving expression of β-cell-specific genes as well as improved localization of GLUT2., (Copyright © 2016 Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
37. Monoclonal antibodies that bind to the Ly6 domain of GPIHBP1 abolish the binding of LPL.
- Author
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Hu X, Sleeman MW, Miyashita K, Linton MF, Allan CM, He C, Larsson M, Tu Y, Sandoval NP, Jung RS, Mapar A, Machida T, Murakami M, Nakajima K, Ploug M, Fong LG, Young SG, and Beigneux AP
- Subjects
- Animals, Binding Sites immunology, Cell Line, Drosophila, Endothelial Cells enzymology, Endothelial Cells immunology, Humans, Lipoprotein Lipase antagonists & inhibitors, Lipoprotein Lipase isolation & purification, Mice, Receptors, Lipoprotein genetics, Triglycerides immunology, Antibodies, Monoclonal immunology, Lipoprotein Lipase immunology, Receptors, Lipoprotein immunology, Triglycerides metabolism
- Abstract
GPIHBP1, an endothelial cell protein, binds LPL in the interstitial spaces and shuttles it to its site of action inside blood vessels. For years, studies of human GPIHBP1 have been hampered by an absence of useful antibodies. We reasoned that monoclonal antibodies (mAbs) against human GPIHBP1 would be useful for 1) defining the functional relevance of GPIHBP1's Ly6 and acidic domains to the binding of LPL; 2) ascertaining whether human GPIHBP1 is expressed exclusively in capillary endothelial cells; and 3) testing whether GPIHBP1 is detectable in human plasma. Here, we report the development of a panel of human GPIHBP1-specific mAbs. Two mAbs against GPIHBP1's Ly6 domain, RE3 and RG3, abolished LPL binding, whereas an antibody against the acidic domain, RF4, did not. Also, mAbs RE3 and RG3 bound with reduced affinity to a mutant GPIHBP1 containing an Ly6 domain mutation (W109S) that abolishes LPL binding. Immunohistochemistry studies with the GPIHBP1 mAbs revealed that human GPIHBP1 is expressed only in capillary endothelial cells. Finally, we created an ELISA that detects GPIHBP1 in human plasma. That ELISA should make it possible for clinical lipidologists to determine whether plasma GPIHBP1 levels are a useful biomarker of metabolic or vascular disease., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
38. Lipoprotein lipase does not increase significantly in the postprandial plasma.
- Author
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Ishiyama N, Sakamaki K, Shimomura Y, Kotani K, Tsuzaki K, Sakane N, Miyashita K, Fukamachi I, Kobayashi J, Stanhope KL, Havel PJ, Kamachi K, Tanaka A, Tokita Y, Machida T, Murakami M, and Nakajima K
- Subjects
- Adolescent, Adult, Dietary Carbohydrates pharmacology, Dietary Fats pharmacology, Drug Interactions, Eating drug effects, Fasting blood, Female, Humans, Lipase blood, Male, Young Adult, Lipoprotein Lipase blood, Postprandial Period drug effects
- Abstract
Background: Previous reports have shown that lipoprotein lipase (LPL) activity significantly increases in the postprandial plasma associated with the increase of TG-rich lipoproteins. Therefore, we have reexamined those relationships using newly developed LPL assay with the different kinds of food intake., Methods: Standard meal (n=81), 50g of fat (n=54), 75g of glucose (n=25) and cookie (25g fat and 75g carbohydrate fat) (n=28) were administered in generally healthy volunteers. Plasma LPL, HTGL and TC, TG, LDL-C, HDL-C, RLP-C and RLP-TG were determined at subsequent withdrawal after the food intake., Results: Plasma TG, RLP-C and RLP-TG were significantly increased at 8PM (2h after dinner of standard meal) compared with 8AM before breakfast within the same day. Also those parameters were significantly increased in 2-6h after fat load. However, the concentrations and activities of LPL and HTGL did not significantly increase in association with an increase in the TG and remnant lipoproteins. Also LPL concentration did not significantly increase after glucose and "cookie test" within 4h., Conclusion: No significant increase of LPL activity was found at CM and VLDL overload after different kinds of food intake when reexamined by newly developed assay for LPL activity and concentration., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
39. Avoidance of Coronary Sinus Injury During Retrograde Cardioplegia.
- Author
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Orihashi K, Miyashita K, Tashiro M, Kihara K, Kondo N, Yamamoto M, Hirose N, Fukutomi T, and Nishimori H
- Subjects
- Echocardiography, Transesophageal, Humans, Coronary Sinus injuries, Heart Arrest, Induced adverse effects
- Abstract
Coronary sinus injury is a rare but critical complication of retrograde cardioplegia. Even after detection, successful repair with a pericardial patch is not always attained. Malalignment of the infusion cannula relative to the coronary sinus is likely to be partially responsible for the injury. Monitoring the location of the cannula tip can help prevent injury. Transesophageal echocardiography can indicate the vascular structure within which the cannula is located. This finding may be useful in preventing injury to the coronary sinus or middle cardiac vein., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
40. The majority of lipoprotein lipase in plasma is bound to remnant lipoproteins: A new definition of remnant lipoproteins.
- Author
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Sato K, Okajima F, Miyashita K, Imamura S, Kobayashi J, Stanhope KL, Havel PJ, Machida T, Sumino H, Murakami M, Schaefer E, and Nakajima K
- Subjects
- Adult, Aged, Diabetes Mellitus, Type 2 blood, Female, Humans, Lactones pharmacology, Lipoprotein Lipase antagonists & inhibitors, Lipoproteins isolation & purification, Male, Metabolic Syndrome blood, Middle Aged, Orlistat, Young Adult, Lipoprotein Lipase blood, Lipoprotein Lipase metabolism, Lipoproteins blood, Lipoproteins metabolism
- Abstract
Background: Lipoprotein lipase (LPL) is a multifunctional protein and a key enzyme involved in the regulation of lipoprotein metabolism. We determined the lipoproteins to which LPL is bound in the pre-heparin and post-heparin plasma., Methods: Tetrahydrolipstatin (THL), a potent inhibitor of serine lipases, was used to block the lipolytic activity of LPL, thereby preventing changes in the plasma lipoproteins due to ex vivo lipolysis. Gel filtration was performed to obtain the LPL elution profiles in plasma and the isolated remnant lipoproteins (RLP)., Results: When ex vivo lipolytic activity was inhibited by THL in the post-heparin plasma, majority of the LPL was found in the VLDL elution range, specifically in the RLP as inactive dimers. However, in the absence of THL, most of the LPL was found in the HDL elution range as active dimers. Furthermore, majority of the LPL in the pre-heparin plasma was found in the RLP as inactive form, with broadly diffused lipoprotein profiles in the presence and absence of THL., Conclusions: It is suggested that during lipolysis in vivo, the endothelial bound LPL dimers generates RLP, forming circulating RLP-LPL complexes in an inactive form that subsequently binds and initiates receptor-mediated catabolism., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
41. An LPL-specific monoclonal antibody, 88B8, that abolishes the binding of LPL to GPIHBP1.
- Author
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Allan CM, Larsson M, Hu X, He C, Jung RS, Mapar A, Voss C, Miyashita K, Machida T, Murakami M, Nakajima K, Bensadoun A, Ploug M, Fong LG, Young SG, and Beigneux AP
- Subjects
- Amino Acid Substitution, Animals, Cell Line, Drosophila melanogaster, Humans, Lipoprotein Lipase genetics, Lipoprotein Lipase metabolism, Mutation, Missense, Protein Binding, Protein Domains, Receptors, Lipoprotein genetics, Receptors, Lipoprotein metabolism, Antibodies, Monoclonal, Murine-Derived chemistry, Lipoprotein Lipase chemistry, Receptors, Lipoprotein chemistry
- Abstract
LPL contains two principal domains: an amino-terminal catalytic domain (residues 1-297) and a carboxyl-terminal domain (residues 298-448) that is important for binding lipids and binding glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1) (an endothelial cell protein that shuttles LPL to the capillary lumen). The LPL sequences required for GPIHBP1 binding have not been examined in detail, but one study suggested that sequences near LPL's carboxyl terminus (residues ∼403-438) were crucial. Here, we tested the ability of LPL-specific monoclonal antibodies (mAbs) to block the binding of LPL to GPIHBP1. One antibody, 88B8, abolished LPL binding to GPIHBP1. Consistent with those results, antibody 88B8 could not bind to GPIHBP1-bound LPL on cultured cells. Antibody 88B8 bound poorly to LPL proteins with amino acid substitutions that interfered with GPIHBP1 binding (e.g., C418Y, E421K). However, the sequences near LPL's carboxyl terminus (residues ∼403-438) were not sufficient for 88B8 binding; upstream sequences (residues 298-400) were also required. Additional studies showed that these same sequences are required for LPL binding to GPIHBP1. In conclusion, we identified an LPL mAb that binds to LPL's GPIHBP1-binding domain. The binding of both antibody 88B8 and GPIHBP1 to LPL depends on large segments of LPL's carboxyl-terminal domain., (Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
42. Preferential expression of CD134, an HHV-6 cellular receptor, on CD4T cells in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS).
- Author
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Miyagawa F, Nakamura Y, Miyashita K, Iioka H, Himuro Y, Ogawa K, Nishimura C, Nishikawa M, Mitsui Y, Ito Y, Ommori R, Mori Y, and Asada H
- Subjects
- Adult, Aged, Aged, 80 and over, Drug Hypersensitivity Syndrome blood, Female, Flow Cytometry, Humans, Male, Middle Aged, CD4-Positive T-Lymphocytes metabolism, Drug Hypersensitivity Syndrome metabolism, Herpesvirus 6, Human metabolism, Receptors, OX40 metabolism
- Published
- 2016
- Full Text
- View/download PDF
43. Acute Progression of Recurrent Meningioma during Luteinizing Hormone-Releasing Hormone Agonist Treatment for Prostate Cancer.
- Author
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Tsutsui T, Miyashita K, Sabit H, Fukui I, Hayashi Y, Mizokami A, Ikeda H, Nagatani H, and Nakada M
- Subjects
- Aged, Cognition Disorders etiology, Disease Progression, Gadolinium pharmacokinetics, Gait Disorders, Neurologic etiology, Humans, Ki-67 Antigen metabolism, Magnetic Resonance Imaging, Male, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms surgery, Meningioma drug therapy, Meningioma surgery, Neoplasm Recurrence, Local diagnostic imaging, Neoplasm Recurrence, Local surgery, Neoplasm, Residual surgery, Prostatic Neoplasms complications, Radiosurgery, Antineoplastic Agents, Hormonal therapeutic use, Leuprolide therapeutic use, Meningeal Neoplasms drug therapy, Neoplasm Recurrence, Local drug therapy, Prostatic Neoplasms drug therapy
- Abstract
Background: Meningiomas are the most common type of benign brain tumor, and the incidence of meningioma in women is more than twofold higher than in men. Several studies have demonstrated that hormones are somehow related to the growth of meningiomas., Case Description: A 72-year-old man with benign meningioma underwent tumor resection and had no recurrence for 18 years. He was found to have prostate cancer, and he received hormonal therapy with a luteinizing hormone-releasing hormone (LHRH) agonist. Two years later, he developed severe cognitive dysfunction and gait disturbance. Gadolinium-enhanced brain magnetic resonance imaging revealed a large recurrent mass and obstructive hydrocephalus. Staged resection was performed and stereotactic radiation therapy was administered against the residual tumor. His symptoms improved after endoscopic third ventriculostomy for obstructive hydrocephalus and his residual tumor remains stable., Conclusions: This is the first report of a case in which an LHRH agonist promoted the growth of a pre-existing meningioma. We suggest that patients with a history of meningioma who are receiving LHRH agonist treatment should be closely monitored., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
44. Ipsilateral hemiparesis in lateral medullary infarction: Clinical investigation of the lesion location on magnetic resonance imaging.
- Author
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Uemura M, Naritomi H, Uno H, Umesaki A, Miyashita K, Toyoda K, Minematsu K, and Nagatsuka K
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Functional Laterality, Humans, Male, Middle Aged, Retrospective Studies, Brain Infarction complications, Brain Infarction diagnostic imaging, Magnetic Resonance Imaging, Medulla Oblongata diagnostic imaging, Paresis diagnostic imaging, Paresis etiology
- Abstract
Background: In 1946, Opalski reported two cases of Wallenberg syndrome with ipsilateral hemiparesis (IH). His hypothesis seems to be based on the view that IH is caused by post-decussating pyramidal tract damage. Afterwards, other researchers proposed a different hypothesis that ipsilateral sensory symptoms of limbs (ISSL) or ipsilateral limb ataxia (ILA) caused by lateral medullary infarction (LMI) might lead to ipsilateral motor weakness. The present study is aimed to clarify whether IH in LMI patients is attributable mainly to ISSL/ILA or disruption of ipsilateral post-decussating pyramidal tract., Methods: Thirty-two patients with acute LMI admitted during the last 13years were divided to IH Group (n=7) and Non-IH Group (n=25). Lesion location/distribution on MRI and neurological findings were compared between the two groups., Results: LMI involved the lower medulla in all seven IH patients and 12 of 25 Non-IH patients. The lower medullary lesion extended to the cervico-medullary junction (CMJ) in four of seven IH patients and one of 12 Non-IH patients. Definitive extension to upper cervical cord (UCC) was confirmed in none of the patients. ISSL was found in two IH and three Non-IH patients all showing only superficial sensory impairments. ILA or hypotonia was observed in 57% of IH and 60% of Non-IH patients., Conclusion: IH in LMI appears to be due mainly to post-decussating pyramidal tract damage at the lower medulla instead of ILA or ISSL participation., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
45. Efficient production of platelets from mouse embryonic stem cells by enforced expression of Gata2 in late hemogenic endothelial cells.
- Author
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Kawaguchi M, Kitajima K, Kanokoda M, Suzuki H, Miyashita K, Nakajima M, Nuriya H, Kasahara K, and Hara T
- Subjects
- Animals, Batch Cell Culture Techniques methods, Blood Platelets metabolism, Cell Differentiation physiology, Cell Proliferation physiology, Cells, Cultured, Embryonic Stem Cells metabolism, Hematopoiesis physiology, Mice, Blood Platelets cytology, Cellular Reprogramming Techniques methods, Embryonic Stem Cells cytology, GATA2 Transcription Factor metabolism, Hemangioblasts cytology, Hemangioblasts metabolism
- Abstract
Platelets are essential for blood circulation and coagulation. Previous study indicated that overexpression of Gata2 in differentiated mouse embryonic stem cells (ESCs) resulted in robust induction of megakaryocytes (Mks). To evaluate platelet production capacity of the Gata2-induced ESC-derived Mks, we generated iGata2-ESC line carrying the doxycycline-inducible Gata2 expression cassette. When doxycycline was added to day 5 hemogenic endothelial cells in the in vitro differentiation culture of iGata2-ESCs, c-Kit(-)Tie2(-)CD41(+) Mks were predominantly generated. These iGata2-ESC-derived Mks efficiently produced CD41(+)CD42b(+)CD61(+) platelets and adhered to fibrinogen-coated glass coverslips in response to thrombin stimulation. Transmission electron microscopy analysis demonstrated that the iGata2-ESC-derived platelets were discoid-shaped with α-granules and an open canalicular system, but were larger than peripheral blood platelets in size. These results demonstrated that an enforced expression of Gata2 in late HECs of differentiated ESCs efficiently promotes megakaryopoiesis followed by platelet production. This study provides valuable information for ex vivo platelet production from human pluripotent stem cells in future., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
46. The Authors Reply.
- Author
-
Tamaki M and Miyashita K
- Subjects
- Animals, Male, Dietary Proteins adverse effects, Exercise Tolerance, Mitochondria, Muscle enzymology, Mitochondrial Turnover, Muscle, Skeletal enzymology, Pyruvate Dehydrogenase Complex metabolism, Renal Insufficiency, Chronic enzymology
- Published
- 2015
- Full Text
- View/download PDF
47. Determination of serum lipoprotein lipase using a latex particle-enhanced turbidimetric immunoassay with an automated analyzer.
- Author
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Machida T, Miyashita K, Sone T, Tanaka S, Nakajima K, Saito M, Stanhope K, Havel P, Sumino H, and Murakami M
- Subjects
- Automation, Blood Chemical Analysis standards, Female, Healthy Volunteers, Humans, Immunoassay standards, Limit of Detection, Linear Models, Male, Nephelometry and Turbidimetry, Reference Values, Young Adult, Blood Chemical Analysis methods, Immunoassay methods, Latex chemistry, Lipoprotein Lipase blood
- Abstract
Background: Lipoprotein lipase (LPL) plays a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides. Quantification of serum LPL is useful for diagnosing lipid disorders, but there is no rapid method of measuring LPL for clinical use., Methods: We developed a rapid and sensitive latex particle-enhanced turbidimetric immunoassay (LTIA) serum LPL using latex bead-immobilized anti-LPL monoclonal antibodies. The assay was performed on a Hitachi 7700 P analyzer and evaluated for its validity as a method of quantitating the serum LPL concentration in parallel with ELISA., Results: Dilution tests using LTIA produced a calibration curve from 0.5 to 800ng/ml. Within-run CV was obtained in the range of 2.2-5.5%. No interference was observed in the testing of specimens containing potentially interfering substances such as bilirubin-F and C, hemoglobin, triglycerides and rheumatoid factor. A strong correlation between LTIA and ELISA was confirmed (n=40, r=0.967, y=0.99x-1.86). The normal range of LPL in pre-heparin serum was 50-77ng/ml and in post-heparin plasma 354-410ng/ml, respectively., Conclusion: The LTIA assay is applicable in quantitating the concentration of LPL in both pre-heparin serum and post-heparin plasma. This assay is more convenient and faster than ELISA and highly suitable for clinical routine analysis., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
48. Genetic alcohol sensitivity regulated by ALDH2 and ADH1B polymorphisms is strongly associated with depression and anxiety in Japanese employees.
- Author
-
Yoshimasu K, Mure K, Hashimoto M, Takemura S, Tsuno K, Hayashida M, Kinoshita K, Takeshita T, and Miyashita K
- Subjects
- Adult, Alcohol-Related Disorders psychology, Aldehyde Dehydrogenase, Mitochondrial, Anxiety Disorders psychology, Asian People psychology, Comorbidity, Depressive Disorder psychology, Female, Humans, Local Government, Male, Middle Aged, Polymorphism, Genetic genetics, Suicidal Ideation, Alcohol Dehydrogenase genetics, Alcohol-Related Disorders genetics, Aldehyde Dehydrogenase genetics, Anxiety Disorders genetics, Asian People genetics, Depressive Disorder genetics, Occupational Health trends
- Abstract
Background: Although alcohol-related disorders (ARD) have been shown to be accompanied by comorbid depressive and anxiety disorders, and alcohol metabolic enzyme genes, ADH1B and ALDH2 polymorphisms, have been associated with an increased risk of ARD, no studies have been conducted to evaluate the associations between these genetic polymorphisms and anxiety or depression., Method: A total of 1944 Japanese workers were interviewed regarding their depressive and anxiety disorders, including suicidality, by a brief psychiatric structured interview (MINI). We investigated the relationship of ADH1B rs1229984 and ALDH2 rs671 polymorphism combinations with mental disorder risks. Logistic regression analysis was used to evaluate the associations between those polymorphisms and anxiety/depressive disorders, adjusting for sex, age, and job rank. The degree of alcohol sensitivity was classified into five groups according to the combination of two enzyme genotypes (Group I-V, in order from the lowest alcohol sensitivity)., Results: Those with ALDH2(*)1/(*)1 and ADH1B(*)1/(*)1 were likely to be at an increased risk of depressive and anxiety disorders as well as ARD. This tendency was more apparent among non-drinkers (OR 9.20, 95% CI 1.66-50.89). No adverse effects of ALDH2 or ADH1B alone were observed with mental disorder risks. Likewise, analyses conducted combining job rank and genetic alcohol sensitivity showed no material associations with such risks., Conclusions: Genetic alcohol sensitivity, especially that with the genotype combination of ALDH2(*)1/(*)1 and ADH1B(*)1/(*)1, was significantly associated with an increased risk of depressive and anxiety disorders as well as ARD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
49. Direct evidence for the causal role of the left supplementary motor area in working memory: A preliminary study.
- Author
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Nakajima R, Okita H, Kinoshita M, Miyashita K, Nakada M, Yahata T, Hamada J, and Hayashi Y
- Subjects
- Adult, Craniotomy, Female, Humans, Male, Neuropsychological Tests, Pilot Projects, Functional Laterality physiology, Glioma surgery, Memory, Short-Term physiology, Monitoring, Intraoperative methods, Motor Cortex pathology, Motor Cortex physiopathology, Motor Cortex surgery, Supratentorial Neoplasms surgery
- Published
- 2014
- Full Text
- View/download PDF
50. Chronic kidney disease reduces muscle mitochondria and exercise endurance and its exacerbation by dietary protein through inactivation of pyruvate dehydrogenase.
- Author
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Tamaki M, Miyashita K, Wakino S, Mitsuishi M, Hayashi K, and Itoh H
- Subjects
- Animals, Cytokines metabolism, Dichloroacetic Acid pharmacology, Dietary Proteins metabolism, Disease Models, Animal, Enzyme Activation, Enzyme Activators pharmacology, Inflammation Mediators metabolism, Male, Mice, Inbred C57BL, Mitochondria, Muscle drug effects, Muscle Strength, Muscle, Skeletal drug effects, Muscle, Skeletal pathology, Muscle, Skeletal physiopathology, Oxidative Stress, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic physiopathology, Renal Insufficiency, Chronic therapy, Running, Signal Transduction drug effects, Time Factors, Dietary Proteins adverse effects, Exercise Tolerance drug effects, Mitochondria, Muscle enzymology, Mitochondrial Turnover drug effects, Muscle, Skeletal enzymology, Pyruvate Dehydrogenase Complex metabolism, Renal Insufficiency, Chronic enzymology
- Abstract
Chronic kidney disease impairs physical performance. Here the time course and mechanism of muscle insufficiency in renal failure and the influence of dietary protein were studied using 5/6 nephrectomized C57Bl/6 mice, focusing on muscle mass and mitochondria. A decrease in muscle mitochondria and running distance was found in young (16-20 weeks) 5/6 nephrectomized mice, despite the preservation of muscle volume and power. However, a decrease in muscle volume, associated with a reduction in muscle power, was found in aged (48-52 weeks) 5/6 nephrectomized mice. A high-protein diet feeding from 8 weeks increased muscle volume and power in the mice; but this further decreased running distance. Activation of pyruvate dehydrogenase by dichloroacetate effectively recovered running distance that was decreased by dietary protein. These findings indicate the mechanism of muscle insufficiency in renal failure and suggest that activation of muscle mitochondria would serve as a potential strategy for improving the physical performance of the patients with chronic kidney disease.
- Published
- 2014
- Full Text
- View/download PDF
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