259 results on '"Toru Miyazaki"'
Search Results
2. Microbiome ssRNA as an environmental cue to activate TLR13-dependent tissue-protective programs in CD5Lhihepatic macrophages
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Ryota Sato, Kaiwen Liu, Takuma Shibata, Katsuaki Hoshino, Kiyoshi Yamaguchi, Toru Miyazaki, Ryosuke Hiranuma, Ryutaro Fukui, Yuji Motoi, Yuri Fukuda-Ohta, Yun Zhang, Tatjana Reuter, Yuko Ishida, Toshikazu Kondo, Tomoki Chiba, Hiroshi Asahara, Masato Taoka, Yoshio Yamauchi, Toshiaki Isobe, Tsuneyasu Kaisho, Yoichi Furukawa, Eicke Latz, and Kensuke Miyake
- Abstract
Hepatic macrophages maintain liver homeostasis, but little is known about the signals that activate the hepatoprotective programs within macrophages. Here, we show that toll-like receptor 13 (TLR13), a sensor of bacterial 23S ribosomal RNA (rRNA), senses microbiome RNAs to drive tissue-protective responses in CD5Lhihepatic macrophages. Splenomegaly and hepatomegaly developed in the absence of the endosomal RNase, RNaseT2, via TLR13-dependent macrophage proliferation. Furthermore, TLR13 in hepatic Ly6Clomacrophages activated the transcription factors LXRα and MafB, leading to expression of tissue-clearance molecules, such as CD5L, C1qb, and Axl. Consequently,Rnaset2−/−mice developed resistance to acute liver injury caused by challenges with acetaminophen and lipopolysaccharide + D-galactosamine. TLR13 responses inRnaset2−/−mice were impaired by antibiotics, suggesting that TLR13 were activated by microbiome rRNAs, which was detected in the sera and hepatic macrophages. Repeated administration of wild-type mice with the TLR13 ligand, rather than other TLR ligands, selectively increased the number of Kupffer cells, which expressed immunoregulatory and tissue-clearance genes as hepatic macrophages inRnaset2−/−mice did. Our results suggest that microbiome ssRNA serves as an environmental cue for initiating tissue-protective TLR13 responses in hepatic macrophages.Graphical AbstractIn the absence of an endosomal RNase, RNase T2, microbiome RNAs circulating in the vasculature activate TLR13 in hepatic macrophages to drive hepatoprotective responses through expression of immunoregulatory and tissue-clearance molecules. Consequently, mice lacking RNase T2 are resistant against acute liver injuries caused by acetaminophen and LPS + D-galactosamine.
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- 2023
3. Two new <scp> JK </scp> silencing alleles identified by single molecule sequencing with <scp>20‐Kb</scp> long‐reads
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Kazumi Isa, Shinnosuke Takada, Hiromi Takeda, Hatsue Tsuneyama, Kenichi Ogasawara, Daisuke Takahashi, Toru Miyazaki, Shigeki Miyata, and Masahiro Satake
- Subjects
Immunology ,Immunology and Allergy ,Hematology - Published
- 2023
4. Baseline inflammatory status affects the prognostic impact of statins in patients with peripheral arterial disease
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Kentaro Jujo, Daisuke Ueshima, Takuro Abe, Kensuke Shimazaki, Yo Fujimoto, Tomofumi Tanaka, Teppei Murata, Toru Miyazaki, Michiaki Matsumoto, Hideo Tokuyama, Tsukasa Shimura, Ryuichi Funada, Naotaka Murata, and Michiaki Higashitani
- Abstract
BackgroundStatins bring favorable effects on the clinical prognosis of patients with atherosclerotic disease partly through their anti-inflammatory properties. However, this effect has not been fully verified in patients with peripheral arterial disease (PAD). We aimed to test whether statins exert different prognostic effects depending on the degrees of inflammation in patients with PAD.MethodsThis study was a sub-analysis of a multicenter prospective cohort of 2,321 consecutive patients with PAD who received endovascular therapy (EVT). After excluding patients without information on C-reactive protein (CRP) levels at the time of index EVT, 1,974 patients (1,021 statin users and 953 non-users) were ultimately analyzed. Enrolled patients were classified into four groups depending on CRP levels: low CRP (1.0 mg/dL). A composite of death, stroke, myocardial infarction, and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category.ResultsOverall, statin users showed a significantly lower event rate than non-users (log-rank, pConclusionStatins may exert favorable prognostic effects in patients with PAD and highly elevated CRP levels but not in those with low to moderate CRP levels.Condensed abstractThis multicenter retrospective study compared the prognostic effects of statins among patients with peripheral arterial disease (PAD) presenting diverse baseline C-reactive protein (CRP) levels [low CRP (1.0 mg/dL)]. Multivariable analysis showed that statin use was independently associated with a lower rate of death, stroke, myocardial infarction, and major amputation only in the high-CRP category. This suggests that statins may have favorable prognostic effects in patients with PAD and active inflammation.
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- 2023
5. Hepatocellular carcinoma diagnosis using a novel electrochemiluminescence immunoassay targeting serum IgM-free AIM
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Tomo, Shimizu, Takashi, Sawada, Tomohide, Asai, Yuka, Kanetsuki, Jiro, Hirota, Michihisa, Moriguchi, Tomoaki, Nakajima, Toru, Miyazaki, and Takeshi, Okanoue
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Immunoassay ,Receptors, Scavenger ,Carcinoma, Hepatocellular ,Macrophages ,Liver Neoplasms ,Gastroenterology ,General Medicine ,digestive system diseases ,Non-alcoholic Fatty Liver Disease ,Biomarkers, Tumor ,Humans ,Prothrombin ,alpha-Fetoproteins ,Apoptosis Regulatory Proteins - Abstract
BackgroundRecent increases in the number of patients with non-alcoholic steatohepatitis (NASH) warrant the identification of biomarkers for early detection of hepatocellular carcinoma (HCC) associated with NASH (NASH-HCC). IgM-free apoptosis inhibitor of macrophage (AIM), which generally associates with IgM in blood and exerts its biological function by dissociation from IgM, may serve as an effective biomarker for NASH-HCC. Here, we established a fully automatic and high-throughput electrochemiluminescence immunoassay (ECLIA) to measure IgM-free AIM and investigated its efficacy in diagnosing NASH-HCC and viral HCC.MethodsIgM-free AIM levels were measured in 212 serum samples from patients with, or without, HCC related to NASH, hepatitis B virus, and hepatitis C virus, using ECLIA. We also developed an ECLIA for measuring both IgM-free and IgM-bound AIM and investigated the existing form of AIM in blood by size-exclusion chromatography.ResultsIgM-free AIM levels were significantly higher in the HCC group than in the non-HCC group, regardless of the associated pathogenesis. Moreover, the area under the receiver operating curve for IgM-free AIM was greater than that for conventional HCC biomarkers, alpha-fetoprotein or des-γ-carboxy prothrombin, regardless of the cancer stage. ECLIA counts of IgM-free AIM derived from samples fractionated by size-exclusion chromatography were significantly higher in patients with NASH-HCC than in healthy volunteers and in patients with non-alcoholic fatty liver and NASH.ConclusionsSerum IgM-free AIM may represent a universal HCC diagnostic marker superior to alpha-fetoprotein or des-γ-carboxy prothrombin. Our newly established ECLIA could contribute to further clinical studies on AIM and in vitro HCC diagnosis.
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- 2022
6. Serum levels of immunoglobulin M-free inhibitors of macrophage/CD5L as a predictive and early diagnostic marker for nonalcoholic steatohepatitis-associated hepatocellular carcinoma
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Takeshi Okanoue, Kanji Yamaguchi, Toshihide Shima, Yasuhide Mitsumoto, Masayuki Mizuno, Takayuki Katayama, Yuya Seko, Michihisa Moriguchi, Atsushi Umemura, Yoshito Itoh, and Toru Miyazaki
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Infectious Diseases ,Hepatology - Abstract
The apoptosis inhibitor of macrophage (AIM) is usually associated with the immunoglobulin M (IgM) pentamer in the blood and is dissociated from IgM in various diseases, including hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH). We aimed to elucidate whether IgM-free AIM (fAIM) is useful for detecting latent HCC in NASH.This research consisted of two cohort studies. The levels of serum fAIM, alpha-fetoprotein (AFP), and des-gamma carboxy prothrombin (DCP) of 18 NASH patients who developed HCC were measured during the follow-up period before HCC diagnosis (median, 4.7 years). In total, 199 patients with nonalcoholic fatty liver disease (NAFLD) were included in the HCC survey. The serum fAIM levels were analyzed using enzyme-linked immunosorbent assays.In the cohort of 18 patients with HCC, 12 had high fAIM at the time of the initial blood sample, three had normal fAIM levels throughout the follow-up period, and three had fAIM elevated from normal to positive. The positive ratio of fAIM prior to HCC diagnosis remained significantly higher than that of AFP and DCP, and the fAIM ratio gradually increased. In a survey of 199 non-HCC NAFLD patients, a Cox regression analysis using independent variables, such as AFP, fAIM, age, albumin, bilirubin, and fibrosis stage, revealed that fAIM and AFP were significantly associated with the incidence of HCC.During the development of NASH-HCC, AIM activation in blood appears to start even before HCC is diagnostically detectable. Thus, the serum IgM-free AIM levels could be a new, sensitive biomarker for latent NASH-HCC.
- Published
- 2022
7. Optimal cut-off value of preprocedural geriatric nutritional risk index for predicting the clinical outcomes of patients undergoing endovascular revascularization for peripheral artery disease
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Masaaki Matsumoto, Hitoshi Anzai, Tsukasa Shimura, Kentaro Jujo, Takahide Kodama, Naotaka Murata, Yo Fujimoto, Kazuki Tobita, Toru Miyazaki, Tetsuo Yamaguchi, Michiaki Higashitani, Yasushi Komatsu, Daisuke Ueshima, Akihiro Matsui, Kenji Suzuki, and Makoto Utsunomiya
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Male ,medicine.medical_specialty ,Endovascular revascularization ,Arterial disease ,Nutritional Status ,Disease ,030204 cardiovascular system & hematology ,Risk Assessment ,Peripheral Arterial Disease ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Predictive Value of Tests ,Reference Values ,Risk Factors ,Internal medicine ,Nutritional risk index ,medicine ,Humans ,Registries ,030212 general & internal medicine ,Geriatric Assessment ,Survival analysis ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Cut off value ,Endovascular Procedures ,Malnutrition ,Critical limb ischemia ,Middle Aged ,Survival Analysis ,Intermittent claudication ,body regions ,Nutrition Assessment ,Preoperative Period ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Malnutrition measured by the geriatric nutritional risk index (GNRI) was reported to be associated with poor prognosis for patients with peripheral artery disease (PAD). However, the optimal cut-off value of preprocedural GNRI for critical limb ischemia (CLI) and intermittent claudication (IC) is unknown. We aimed to determine its optimal cut-off value for CLI or IC patients requiring endovascular revascularization.We explored data of 2246 patients (CLI: n = 1061, IC: n = 1185) registered in the Tokyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry, which prospectively enrolled consecutive PAD patients who underwent endovascular revascularization in 34 hospitals in Japan from August 2014 to August 2016. The optimal cut-off values of GNRI were assessed by the survival classification and regression tree (CART) analyses, and the survival curve analyses for major adverse cardiovascular and limb events (MACLEs) were performed for these cut-off values.In addition to the first cut-off value of 96.2 in CLI and 85.6 in IC, the survival CART provided an additional cut-off value of 78.2 in CLI and 106.0 in IC for further risk stratification. The survival curve was significantly stratified by the GNRI-based malnutrition status in both CLI [high risk: 47.7% (51/107), moderate: 30.1% (118/392), and low: 10.2% (53/520), log-rank p 0.001] and IC [high risk: 14.3% (7/49), moderate: 4.5% (29/646), and low: 0.5% (2/407), log-rank p 0.001]. The multivariate Cox-proportional hazard analysis showed that a higher GNRI was significantly associated with a better outcome in both CLI [hazard ratio (HR) per 1-point increase: 0.97, 95% CI: 0.96-0.98, p 0.001] and IC (HR: 0.94, 95% CI: 0.91-0.97, p 0.001).Preprocedural nutritional status significantly stratified future events in patients with PAD. Given that the optimal cut-off value of GNRI in CLI was almost 10-points lower than that of IC, using a disease-specific cut-off value is important for risk stratification.
- Published
- 2021
8. Precancerous Lesions and Liver Atrophy as Risk Factors for Hepatolithiasis-Related Death after Liver Resection for Hepatolithiasis
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Atsushi Ishihara, Daisuke Shirai, Shigekazu Takemura, Kenichi Wakasa, Kenjiro Kimura, Takatsugu Yamamoto, Toru Miyazaki, Masahiko Kinoshita, Jun Tsuchi, Ryosuke Amano, Shogo Tanaka, Kohei Nishio, Shimpei Eguchi, Hiroji Shinkawa, Shoji Kubo, Go Ohira, and Norifumi Kawada
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liver atrophy ,Male ,0301 basic medicine ,medicine.medical_specialty ,Biliary cirrhosis ,Lithiasis ,biliary intraepithelial neoplasia ,Gastroenterology ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Hepatectomy ,Humans ,Pathological ,Aged ,Univariate analysis ,Bile duct ,business.industry ,Liver Diseases ,hepatolithiasis ,General Medicine ,Jaundice ,Prognosis ,medicine.disease ,Survival Rate ,030104 developmental biology ,medicine.anatomical_structure ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Concomitant ,Biliary Intraepithelial Neoplasia ,Female ,Atrophy ,Hepatolithiasis ,medicine.symptom ,business ,Precancerous Conditions ,Research Article ,Follow-Up Studies - Abstract
Background Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. Methods The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P. Results In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively. Conclusions Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors. .
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- 2020
9. Five-Year Impacts of Antithrombotic Therapy Based on 10-Year Clinical Outcomes of Cypher™ Stent Implantation
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Ken Kurihara, Shiho Kawamoto, Ayaka Kimura, Akifumi Tanaka, Kento Yabe, Hidetsugu Nomoto, Yuki Osaka, Toru Miyazaki, Asami Suzuki, Yuichi Ono, Kenichiro Otomo, and Tetsuo Sasano
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Cardiology and Cardiovascular Medicine - Abstract
Few researchers have investigated the optimal long-term antithrombotic therapy regimen, especially after first-generation drug-eluting stent (DES) use. This study aimed to evaluate the impact of mid-term antithrombotic therapy on long-term outcomes in patients treated with the first sirolimus-eluting coronary stent (Cypher™).Between 2004 and 2009, 1021 patients underwent Cypher™ implantation at our institute; among them, 567 patients had available data on antithrombotic therapy at year 5. We assessed patients' antithrombotic therapy at year 5 post Cypher™ implantation and examined their association with adverse events from year 5 to year 10 post Cypher™ implantation.Patients with dual-antiplatelet therapy (DAPT) at year 5 had significantly lower risk of stent thrombosis (ST) than those with single-antiplatelet therapy (SAPT) (hazard ratio [HR] 0.24, p = 0.034). The HR of major bleeding in DAPT, compared to SAPT, was high, but the difference was not significant (HR 1.72, p = 0.26). Risk of major bleeding was significantly higher in patients on oral anticoagulants (OAC) than in those in other groups (OAC/SAPT; HR 5.31, p = 0.0048, OAC/DAPT; HR 3.08, p = 0.022), without significant reduction in the risk of cardiovascular events.The incidence of ST after Cypher™ implantation in patients with DAPT at year 5 was significantly lower than that in SAPT. However, the risk of bleeding was higher with DAPT than with SAPT. Moreover, the risk of major bleeding was significantly higher in patients on anticoagulant therapy than in other patients. New options for the use of antithrombotic drugs after percutaneous coronary intervention warrant further studies on the optimal antithrombotic therapy for first-generation DES.
- Published
- 2022
10. Impact of the Preoperative C-reactive Protein to Albumin Ratio on the Long-Term Outcomes of Hepatic Resection for Intrahepatic Cholangiocarcinoma
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Toru Miyazaki, Takayoshi Nishioka, Atsushi Ishihara, Shigekazu Takemura, Tokuji Ito, Hiroji Shinkawa, Shogo Tanaka, and Shoji Kubo
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Multivariate analysis ,Hepatic resection ,hepatic resection ,Gastroenterology ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,intrahepatic cholangiocarcinoma ,Internal medicine ,Preoperative Care ,Biomarkers, Tumor ,medicine ,Long term outcomes ,Hepatectomy ,Humans ,prognostic factor ,Serum Albumin ,CRP/Alb ratio ,Intrahepatic Cholangiocarcinoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,Univariate analysis ,biology ,business.industry ,C-reactive protein ,Albumin ,General Medicine ,Middle Aged ,Prognosis ,Survival Rate ,C-Reactive Protein ,030104 developmental biology ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Positive Surgical Margin ,business ,Follow-Up Studies ,Research Article - Abstract
Objective: The present study aimed to investigate the impact of preoperative C-reactive protein to albumin (CRP/Alb) ratio on the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC). Methods: 82 patients who underwent hepatic resection for mass-forming type of ICC were evaluated. The relationship between preoperative CRP/Alb ratio and survival outcomes was investigated. Results: The optimal cutoff value of CRP/Alb ratio for assessing overall survival (OS) was determined as 0.089. Univariate analysis for recurrence-free survival (RFS) showed that CRP/Alb ratio >0.089, carbohydrate antigen 19-9 (CA 19-9) >37 U/mL, lymph node metastasis, vascular invasion, and multiple tumors were significantly associated with postoperative recurrence. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.006), and multiple tumors (p < 0.001). Univariate analysis for OS showed that CRP/Alb ratio >0.089, CA 19-9 >37 U/mL, lymph node metastasis, vascular invasion, multiple tumors, and positive surgical margin were significantly associated with overall death. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.01), and multiple tumors (p = 0.005). Conclusion: Preoperative CRP/Alb ratio may predict poor long-term outcomes after hepatic resection in patients with ICC.
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- 2020
11. Crucial Role of AIM/CD5L in the Development of Glomerular Inflammation in IgA Nephropathy
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Yusuke Suzuki, Rina Kato, Emiri Hiramoto, Satoko Arai, Kimi Araki, Hitoshi Suzuki, Yuko Makita, Junichiro Nakata, Toru Miyazaki, Akiko Takahata, and Kento Kitada
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Kidney Glomerulus ,Inflammation ,urologic and male genital diseases ,Immune complex formation ,law.invention ,Nephropathy ,Mice ,Downregulation and upregulation ,law ,medicine ,Animals ,Humans ,Complement Activation ,Receptors, Scavenger ,Mice, Inbred BALB C ,Proteinuria ,business.industry ,Glomerulonephritis, IGA ,General Medicine ,medicine.disease ,Phenotype ,Immunoglobulin A ,Basic Research ,Nephrology ,Immunology ,Recombinant DNA ,medicine.symptom ,Apoptosis Regulatory Proteins ,business ,Infiltration (medical) - Abstract
Background IgA nephropathy (IgAN) begins with aberrant IgA deposition in glomeruli, progresses to IgM/IgG/complement codeposition, and results in chronic inflammation and glomerular damage. However, the mechanism that drives such phlogogenic cascade has been unclear. Recently, apoptosis inhibitor of macrophage (AIM) protein was shown to modulate macrophages' function in various pathologic conditions, thereby profoundly affecting the progression of renal disorders, including AKI. A spontaneous IgAN model, grouped ddY (gddY) mouse, revealed the requirement of AIM for the overall inflammatory glomerular injury following IgA deposition. Methods We established an AIM-deficient IgAN model (AIM -/- gddY) using CRISPR/Cas9 and compared its phenotype with that of wild-type gddY with or without recombinant AIM administration. An IgA-deficient IgAN model (IgA -/- gddY) was also generated to further determine the role of AIM. Results In both human and murine IgAN, AIM colocalized with IgA/IgM/IgG in glomeruli, whereas control kidneys did not exhibit AIM deposition. Although AIM -/- gddY showed IgA deposition at levels comparable with those of wild-type gddY, they did not exhibit glomerular accumulation of IgM/IgG complements, CD45+ leukocyte infiltration, and upregulation of inflammatory/fibrogenic genes, indicating protection from glomerular lesions and proteinuria/hematuria. Recombinant AIM administration reconstituted the IgAN phenotype, resulting in IgM/IgG/complement IgA codeposition. Neither spontaneous IgM/IgG codeposition nor disease was observed in IgA -/- gddY mice. Conclusions AIM may contribute to stable immune complex formation in glomeruli, thereby facilitating IgAN progression. Therefore, AIM deposition blockage or disassociation from IgM/IgG may present a new therapeutic target on the basis of its role in IgAN inflammation initiation.
- Published
- 2020
12. A new antigen <scp>SUMI</scp> carried on glycophorin <scp>A</scp> encoded by the <scp> GYPA*M </scp> with c. <scp>91A></scp> C (p. <scp>Thr31Pro</scp> ) belongs to the <scp>MNS</scp> blood group system
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Kenichi Ogasawara, Toru Miyazaki, Kazumi Isa, Ryo Kurita, Hatsue Tsuneyama, Masahiro Satake, Go Kikuchi, Makoto Uchikawa, Sayaka Kaito, and Shoichi Ito
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Sanger sequencing ,GYPA ,biology ,GYPB ,Chemistry ,Immunology ,Hematology ,030204 cardiovascular system & hematology ,MNS antigen system ,Molecular biology ,03 medical and health sciences ,Red blood cell ,symbols.namesake ,0302 clinical medicine ,medicine.anatomical_structure ,Antigen ,biology.protein ,medicine ,symbols ,Immunology and Allergy ,Glycophorin ,Antibody ,030215 immunology - Abstract
Background MNS is one of the highly polymorphic blood groups comprising many antigens generated by genomic recombination among the GYPA, GYPB, and GYPE genes as well as by single-nucleotide changes. We report a patient with red blood cell (RBC) antibody against an unknown low-frequency antigen, tentatively named SUMI, and investigated its carrier molecule and causal gene. Study design and methods Standard serologic tests, including enzyme tests, were performed. Monoclonal anti-SUMI-producing cells (HIRO-305) were established by transformation and hybridization methods using lymphocytes from a donor having anti-SUMI. SUMI+ RBCs were examined by immunocomplex capture fluorescence analysis (ICFA) using HIRO-305 and murine monoclonal antibodies against RBC membrane proteins carrying blood group antigens. Genomic DNA was extracted from whole blood, and the GYPA gene was analyzed by polymerase chain reactions and Sanger sequencing. Results Serologic screening revealed that 23 of the 541,522 individuals (0.0042%) were SUMI+, whereas 1351 of the 10,392 individuals (13.0%) had alloanti-SUMI. SUMI antigen was sensitive to ficin, trypsin, pronase, and neuraminidase, but resistant to α-chymotrypsin and sulfydryl-reducing agents. ICFA revealed that the SUMI antigen was carried on glycophorin A (GPA). According to Sanger sequencing and cloning, the SUMI+ individuals had a GYPA*M allele with c.91A>C (p.Thr31Pro), which may abolish the O-glycan attachment site. Conclusions The new low-frequency antigen SUMI is carried on GPA encoded by the GYPA*M allele with c.91A>C (p.Thr31Pro). Neuraminidase sensitivity suggests that glycophorin around Pro31 are involved in the SUMI determinant.
- Published
- 2020
13. Long-Term Efficacy and Safety of Everolimus-Eluting Stent Implantation in Japanese Patients with Acute Coronary Syndrome: Five-Year Real-World Data from the Tokyo-MD PCI Study
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Ken Kurihara, Takashi Ashikaga, Toru Miyazaki, Kenzo Hirao, and Shunji Yoshikawa
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Male ,lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,Acute coronary syndrome ,Article Subject ,medicine.medical_treatment ,Myocardial Infarction ,Coronary Artery Disease ,Cohort Studies ,Coronary artery disease ,Percutaneous Coronary Intervention ,Japan ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Cumulative incidence ,Everolimus ,Registries ,Myocardial infarction ,Acute Coronary Syndrome ,Aged ,business.industry ,Hazard ratio ,Percutaneous coronary intervention ,Stent ,Drug-Eluting Stents ,Thrombosis ,Middle Aged ,medicine.disease ,lcsh:RC666-701 ,Conventional PCI ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Research Article - Abstract
Background. The long-term safety of first-generation drug-eluting stent (DES) in acute coronary syndrome (ACS) was controversial. Purpose. The purpose of this study was to establish 5-year real-world data regarding the long-term efficacy and safety of second-generation DES in Japanese patients with ACS. Methods. The Tokyo-MD PCI study is a multicenter, observational cohort study enrolling consecutive patients who underwent everolimus-eluting stent (EES) implantation. The 5-year clinical events were compared between the ACS group (n = 644) and the stable coronary artery disease (SCAD) group (n = 1255). The primary efficacy endpoint was ischemia-driven target lesion revascularization (TLR), and the primary safety endpoint was the composite of all-cause death or myocardial infarction (MI). Results. The median follow-up duration was 5.4 years. The cumulative incidence of ischemia-driven TLR was similar between ACS and SCAD (1 year: 3.0% versus 2.7%; P=0.682, 1–5 years: 2.7% versus 2.9%; P=0.864). The cumulative incidence of all-cause death or MI within 1 year was significantly higher in ACS than in SCAD (7.4% versus 3.8%; P<0.001); however, ACS did not increase the risk of all-cause death or MI after adjusting confounders (adjusted hazard ratio, 1.260; 95% confidence interval, 0.774–2.053; P=0.352). From 1 to 5 years, the cumulative incidence of all-cause death or MI was not significantly different between ACS and SCAD (11.6% versus 11.4%; P=0.706). The cumulative incidence of very late stent thrombosis was low and similar between ACS and SCAD (0.2% versus 0.2%; P=0.942). Conclusion. This real-world registry suggested that EES has comparable long-term efficacy and safety in patients with ACS and SCAD.
- Published
- 2019
14. Recessive mutation in CD2AP causes focal segmental glomerulosclerosis in humans and mice
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Lamine Aoudjit, Toru Miyazaki, Indra R. Gupta, Cindy Baldwin, Eric Bareke, Tomoko Takano, Philip Pisano, Ken Ichi Yamamura, Jun Matsuda, Jasmine El Andalousi, Lina Muhtadie, Chantal Bernard, Naoki Takeda, and Jacek Majewski
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,030232 urology & nephrology ,Mice, Transgenic ,urologic and male genital diseases ,Frameshift mutation ,End stage renal disease ,Consanguinity ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Human disease ,Focal segmental glomerulosclerosis ,Exome Sequencing ,Animals ,Humans ,Medicine ,In patient ,Gene Knock-In Techniques ,Frameshift Mutation ,Adaptor Proteins, Signal Transducing ,Gene Editing ,Kidney ,Glomerulosclerosis, Focal Segmental ,urogenital system ,business.industry ,Homozygote ,Conclusive evidence ,medicine.disease ,female genital diseases and pregnancy complications ,Pedigree ,Cytoskeletal Proteins ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Nephrology ,Mutation (genetic algorithm) ,Disease Progression ,Kidney Failure, Chronic ,Female ,business - Abstract
Although sequence variants in CD2-associated protein (CD2AP) have been identified in patients with focal segmental glomerulosclerosis (FSGS), definitive proof of causality in human disease is meager. By whole-exome sequencing, we identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. These results provide conclusive evidence that homozygous mutation of CD2AP causes FSGS in humans.
- Published
- 2019
15. AIM/CD5L attenuates DAMPs in the injured brain and thereby ameliorates ischemic stroke
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Ami Okuno, Satoko Arai, Zhiheng Li, Ching-Ting Wang, Toru Miyazaki, Aika Hirota, Kaori Taniguchi, Natsumi Maehara, and Hideaki Ando
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Male ,Phagocyte ,QH301-705.5 ,Interleukin-1beta ,MafB Transcription Factor ,Inflammation ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,medicine ,Animal mortality ,Alarmins ,Animals ,Humans ,Disulfides ,Scavenger receptor ,Biology (General) ,Receptor ,Stroke ,Ischemic Stroke ,Mice, Knockout ,Receptors, Scavenger ,apoptosis inhibitor of macrophage (AIM)/CD5 antigen-like (CD5L) ,business.industry ,Interleukin-6 ,Macrophages ,Pattern recognition receptor ,pattern recognition receptors ,phagocyte ,Brain ,respiratory system ,medicine.disease ,Prognosis ,Recombinant Proteins ,body regions ,Mice, Inbred C57BL ,Survival Rate ,Disease Models, Animal ,medicine.anatomical_structure ,sterile inflammation ,Ischemic stroke ,damage-associated molecular patterns (DAMPs) ,medicine.symptom ,business ,Apoptosis Regulatory Proteins ,Protein Binding - Abstract
Summary: The sterile inflammation caused by damage-associated molecular patterns (DAMPs) worsens the prognosis following primary injury such as ischemic stroke. However, there are no effective treatments to regulate DAMPs. Here, we report that AIM (or CD5L) protein reduces sterile inflammation by attenuating DAMPs and that AIM administration ameliorates the deleterious effects of ischemic stroke. AIM binds to DAMPs via charge-based interactions and disulfide bond formation. This AIM association promotes the phagocytic removal of DAMPs and neutralizes DAMPs by impeding their binding to inflammatory receptors. In experimental stroke, AIM-deficient mice exhibit severe neurological damage and higher mortality with greater levels of DAMPs and associated inflammation in the brain than wild-type mice, in which brain AIM levels increase following stroke onset. Recombinant AIM administration reduces sterile inflammation in the infarcted region, leading to a profound reduction of animal mortality. Our findings provide a basis for the therapies targeting DAMPs to improve ischemic stroke.
- Published
- 2021
16. Durable response after discontinuation of pembrolizumab therapy for intrahepatic cholangiocarcinoma: a case report
- Author
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Kenjiro Kimura, Yasunori Sato, Atsushi Ishihara, Go Ohira, Toru Miyazaki, Shoji Kubo, Shogo Tanaka, Jun Tauchi, Shimpei Eguchi, Hiroji Shinkawa, Kozo Nakai, Shigekazu Takemura, Kohei Nishio, Ryosuke Amano, Daisuke Shirai, and Masahiko Kinoshita
- Subjects
medicine.medical_specialty ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,medicine ,Humans ,Lymph node ,Intrahepatic Cholangiocarcinoma ,business.industry ,Liver Neoplasms ,Microsatellite instability ,General Medicine ,Hepatology ,medicine.disease ,Discontinuation ,medicine.anatomical_structure ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Bullous pemphigoid ,Neoplasm Recurrence, Local ,business - Abstract
Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19-9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma.
- Published
- 2021
17. Correction to: Hepatocellular carcinoma diagnosis using a novel electrochemiluminescence immunoassay targeting serum IgM‑free AIM
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Tomo Shimizu, Takashi Sawada, Tomohide Asai, Yuka Kanetsuki, Jiro Hirota, Michihisa Moriguchi, Tomoaki Nakajima, Toru Miyazaki, and Takeshi Okanoue
- Subjects
Gastroenterology ,General Medicine - Published
- 2022
18. Incidence of outflow tract ventricular tachycardia long after surgical aortic valve replacement
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Yoshihide Takahashi, Hidetsugu Nomoto, Ken Kurihara, Kentaro Goto, Yuichi Ono, Tetsuo Sasano, Masahiko Goya, Asami Suzuki, Takeshi Someya, Kenichiro Otomo, Yuki Osaka, and Toru Miyazaki
- Subjects
medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,030204 cardiovascular system & hematology ,Ventricular tachycardia ,arrhythmia ,03 medical and health sciences ,0302 clinical medicine ,Aortic valve replacement ,Cardiac magnetic resonance imaging ,Internal medicine ,medicine ,periaortic ,aortic valve replacement ,030212 general & internal medicine ,cardiovascular diseases ,Systole ,Ejection fraction ,Bundle branch block ,medicine.diagnostic_test ,business.industry ,Original Articles ,medicine.disease ,Signal-averaged electrocardiogram ,medicine.anatomical_structure ,Ventricle ,lcsh:RC666-701 ,Cardiology ,cardiovascular system ,Original Article ,long term ,ventricular tachycardia ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background The peri‐outflow tract region could be the origin of ventricular tachycardia (VT) after aortic valve replacement (AVR). However, the clinical characteristics of outflow tract ventricular tachycardias (OTVTs) after AVR are yet to be clarified. This study investigated the incidence, risk factors, and clinical characteristics of patients with OTVTs after AVR. Methods We retrospectively analyzed the clinical course of 120 patients who had undergone surgical AVR (SAVR) between April 1980 and October 2018. The patients had no ischemic or diagnosed cardiomyopathies other than primary aortic valve diseases. Results Six patients (5.0%) developed OTVTs after SAVR. The average onset was at 10.8 ± 5.7 years after SAVR. All cases of VT arose from the inferior axis and included left and right bundle branch block configuration. Two patients who underwent cardiac magnetic resonance imaging (MRI) had late gadolinium enhancement (LGE) in the midlayer of the left ventricle basal anteroseptal wall. Patients with periaortic VTs had significantly larger left ventricular (LV) diameter at systole, lower LV ejection fraction, higher positive rates of signal‐averaged electrocardiogram (SAECG), and nonsustained VTs on Holter monitoring. On ablation, local fragmented potentials with low voltage zones were observed in accordance with the LGE distribution. Multiple VTs originating from the periaortic region were provoked in the sessions. Conclusions Acute OTVT was found in 5% of patients after SAVR. Arrhythmia risk stratification by SAECG, Holter ECG, and cardiac MRI should be considered for a long period in patients after SAVR., Based on our results, acute onset of OTVT was found in 5% of patients who received SAVR. Therefore, we suggest that arrhythmic risk stratification should be considered for patients who have undergone SAVR for a long period.
- Published
- 2020
19. Predictive Value of the Age-Adjusted Charlson Comorbidity Index for Outcomes After Hepatic Resection of Hepatocellular Carcinoma
- Author
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Takayoshi Nishioka, Kenjiro Kimura, Hiroji Shinkawa, Shigekazu Takemura, Toru Miyazaki, Shoji Kubo, Shogo Tanaka, and Ryosuke Amano
- Subjects
medicine.medical_specialty ,Carcinoma, Hepatocellular ,Age adjustment ,Comorbidity ,030230 surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Hepatectomy ,Humans ,Retrospective Studies ,business.industry ,Hazard ratio ,Liver Neoplasms ,Age Factors ,Odds ratio ,Vascular surgery ,medicine.disease ,Cardiac surgery ,Cardiothoracic surgery ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Surgery ,Neoplasm Recurrence, Local ,business ,Abdominal surgery - Abstract
This study aimed to evaluate the impact of the age-adjusted Charlson comorbidity index (ACCI) on outcomes after hepatic resection for hepatocellular carcinoma (HCC). We assessed 763 patients who underwent hepatic resection for HCC. The ACCI scores were categorized as follows: ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7. A multivariate analysis showed that the odds ratios for postoperative complications in ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 0.71 (p = 0.41) and 4.15 (p
- Published
- 2020
20. Prognostic value of expanded liver transplantation criteria-the 5-5-500 rule-in patients with hepatic resection for intermediate-stage hepatocellular carcinoma
- Author
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Kenjiro Kimura, Shoji Kubo, Shigekazu Takemura, Toru Miyazaki, Hiroji Shinkawa, Ryosuke Amano, Shogo Tanaka, and Masahiko Kinoshita
- Subjects
medicine.medical_specialty ,Cirrhosis ,Carcinoma, Hepatocellular ,Hepatic resection ,medicine.medical_treatment ,Liver transplantation ,Gastroenterology ,Intermediate stage ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Hepatectomy ,Humans ,In patient ,Neoplasm Staging ,Retrospective Studies ,Hepatology ,Tumor size ,business.industry ,Liver Neoplasms ,Infant, Newborn ,medicine.disease ,Prognosis ,Liver Transplantation ,Treatment Outcome ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Surgery ,Liver cancer ,business - Abstract
Background This study aimed to evaluate the prognostic impact of the 5-5-500 rule in patients after hepatic resection for the intermediate stage of hepatocellular carcinoma (HCC; The Barcelona Clinic Liver Cancer classification [BCLC] B). Methods 177 patients had hepatic resection for BCLC-B HCC. The 5-5-500 rule was defined by tumor size ≤5 cm in diameter, tumor number ≤5, and α-fetoprotein ≤500 ng/mL. Results The 3-, 5-, and 7-year recurrence-free survival rates were 22%, 14%, and 11% in patients within the 5-5-500 rule, and 16%, 10%, and 10% in patients beyond the 5-5-500 rule, respectively (P = .015). The 3-, 5-, and 7-year overall survival rates were 72%, 47%, and 34% in patients within the 5-5-500 rule, and 52%, 31%, and 25% in patients beyond the 5-5-500 rule, respectively (P = .035). Being beyond the 5-5-500 rule and liver cirrhosis were independent prognostic factors for recurrence-free survival. For overall survival, being beyond the 5-5-500 rule, age ≥65 years, Child-Pugh class B, and anti-hepatitis C antibody positive were identified as independent prognostic factors. Conclusions The 5-5-500 rule could predict prognosis in BCLC-B patients with hepatic resection. Hepatic resection might provide survival benefit for selected patients with BCLC-B HCC within the 5-5-500 rule.
- Published
- 2020
21. The B allele with a 5·8 kb deletion in intron 1 of the ABO gene is the major allele in Japanese individuals with Bm and A1 Bm phenotypes
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N. Yokoya, Yuji Hori, Toru Miyazaki, Makoto Uchikawa, Takayuki Enomoto, Shoichi Ito, Masahiro Satake, Kenichi Ogasawara, Ryuichi Yabe, M. Kumamoto, and S. Watanabe
- Subjects
Intron ,Hematology ,General Medicine ,030204 cardiovascular system & hematology ,Biology ,Molecular biology ,Phenotype ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Transcription (biology) ,ABO blood group system ,Allele ,Enhancer ,030215 immunology - Abstract
Bm and A1 Bm phenotypes are the most frequent ABO variants in the Japanese population. The B antigen on Bm red blood cells is only detectable by adsorption and elution tests, and plasma B-transferase activity is usually detected at half or less levels compared with that of common B. Recently, a B allele lacking an erythroid cell-specific transcription enhancer in intron 1 of the ABO gene was identified from individuals with Bm and A1 Bm phenotypes, which could explain the unique serologic properties of Bm . In the Japanese Red Cross Society, eight Blood Centers tested blood samples from donors throughout Japan and collected blood samples from 888 Bm and 415 A1 Bm individuals. DNA analysis revealed that 1300 of 1303 (99·77%) individuals had the B allele with a 5·8 kb deletion (c.28 + 5110_10889del), which included the enhancer element.
- Published
- 2018
22. AIM associated with the IgM pentamer: attackers on stand-by at aircraft carrier
- Author
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Tomoko Yamazaki, Satoko Arai, Ryoichi Sugisawa, M. Eric Gershwin, and Toru Miyazaki
- Subjects
0301 basic medicine ,Aircraft ,Immunology ,Antigen presentation ,Apoptosis ,Kidney ,Article ,03 medical and health sciences ,Immune system ,Antigen ,Diabetes Mellitus ,Animals ,Humans ,Immunology and Allergy ,Diabetic Nephropathies ,Autoantibodies ,Receptors, Scavenger ,Follicular dendritic cells ,biology ,Chemistry ,Macrophages ,Comment ,Germinal center ,Acute Kidney Injury ,IgM binding ,Immune complex ,030104 developmental biology ,Infectious Diseases ,Immunoglobulin M ,Disease Progression ,biology.protein - Abstract
Circulating immunoglobulin M (IgM) exists in a pentameric form, possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens; thus, it is involved in both beneficial and detrimental immune responses, including protection from infection and the progression of autoimmunity. On the other hand, IgM also behaves as a carrier of the apoptosis inhibitor of macrophage (AIM) protein, storing a large amount of the inactivated form of AIM in the blood through this association. Under different disease conditions, AIM can dissociate from IgM locally or systemically to exert its function, inducing the removal of various biological debris such as excess fat, bacteria, cancer cells or dead cell debris. Most typically, upon induction of acute kidney injury (AKI), IgM-free AIM is filtered by the glomerulus in the kidney, which stimulates the clearance of intraluminal dead cells debris at the obstructed proximal tubules, thereby facilitating the repair of kidney injury. Interestingly, cats exhibit a deficiency in AIM release from IgM, which may increase their susceptibility to renal failure. Conversely, association with AIM inhibits IgM binding to the Fcα/μ receptor on follicular dendritic cells at the splenic germinal center, thereby protecting the IgM immune complex from Fcα/μ receptor-mediated internalization, which supports IgM-dependent antigen presentation to B cells and stimulates high-affinity IgG antibody production. The regulation of AIM-IgM binding, resulting from the discovery of reciprocal actions between AIM and IgM, could lead to the development of novel therapies against different diseases.
- Published
- 2018
23. Skin Metastasis of Upper Trunk, Neck and Head Skin One Year after Distal Gastrectomy for Early Gastric Cancer
- Author
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Masato Okawa, Kazuhisa Kaneda, Chie Watanabe, Shogo Tanaka, Takahiro Uenishi, Kenichi Wakasa, Koichi Ohno, Toru Miyazaki, Hiromu Tanaka, and Takatsugu Yamamoto
- Subjects
medicine.medical_specialty ,medicine.anatomical_structure ,Upper trunk ,business.industry ,Distal gastrectomy ,medicine ,Head (vessel) ,business ,Skin metastasis ,Surgery ,Early Gastric Cancer - Published
- 2018
24. Orchestrating Role of Apoptosis Inhibitor of Macrophage in the Resolution of Acute Lung Injury
- Author
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Takahide Nagase, Hideo Shindou, Toru Miyazaki, Masaru Suzuki, Masaharu Nishimura, Satoshi Konno, Hiroki Kimura, and Takao Shimizu
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Neutrophils ,Acute Lung Injury ,Immunology ,Apoptosis ,Inflammation ,Pharmacology ,Biology ,Lung injury ,Mice ,03 medical and health sciences ,Phagocytosis ,medicine ,Animals ,Immunology and Allergy ,Macrophage ,Receptors, Immunologic ,Efferocytosis ,Cells, Cultured ,Tissue homeostasis ,Mice, Knockout ,Receptors, Scavenger ,medicine.diagnostic_test ,Macrophages ,Lipid metabolism ,Lipid signaling ,Lipid Metabolism ,Mice, Inbred C57BL ,030104 developmental biology ,Bronchoalveolar lavage ,medicine.symptom ,Apoptosis Regulatory Proteins - Abstract
Appropriate resolution of inflammation is known to be essential in tissue homeostasis. In this study, we evaluated the significance of a macrophage-derived soluble protein, apoptosis inhibitor of macrophage (AIM), in LPS-induced lung injury in mice. After oropharyngeal administration of LPS, the level of free-form serum AIM increased on days 2–4, accompanied by the resolution of inflammation, which was observed in the cellular profile of bronchoalveolar lavage fluid. In an experiment using wild-type (WT) and AIM−/− mice, the resolution of inflammation was accelerated in AIM−/− mice when compared with the WT mice, which was reversed when recombinant AIM protein was administered. The changes in the histopathological findings and inflammatory mediators followed similar trends, and the ratio of apoptotic cells was increased in AIM−/− mice when compared with the WT mice. In vitro analysis showed that macrophage phagocytosis of apoptotic neutrophils was suppressed in the presence of AIM, indicating that anti-resolution property of AIM involves efferocytosis inhibition. In lipidomic analysis of lung tissues, the levels of several lipid mediators increased markedly when LPS was given to WT mice. However, in AIM−/− mice, the concentrations of these lipid mediators were not significantly upregulated by LPS. These data reflect the significant role of AIM in lipid metabolism; it may suppress lipid metabolites at baseline, and then produce an inflammatory/pathologic pattern in the event of LPS-induced lung injury. Taken together, AIM may play an orchestrating role in the resolution process of inflammation by altering the profile of pulmonary lipid mediators in mice.
- Published
- 2017
25. Establishment of a novel cell-based assay using HLA-transfected cells to detect HLA antibodies
- Author
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Toru Miyazaki, Shuichi Kino, Shinichiro Sato, Daisuke Takahashi, Hisami Ikeda, Manabu Nakano, and Katsuya Ikuta
- Subjects
0301 basic medicine ,Antigenicity ,Time Factors ,Immunology ,Fluorescent Antibody Technique ,Human leukocyte antigen ,Lung injury ,Transfection ,Peripheral blood mononuclear cell ,Antibodies ,Specimen Handling ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Predictive Value of Tests ,Humans ,Immunology and Allergy ,Cryopreservation ,HLA-A Antigens ,biology ,Chemistry ,Histocompatibility Testing ,Reproducibility of Results ,Molecular biology ,Platelet transfusion refractoriness ,HEK293 Cells ,030104 developmental biology ,Cell culture ,biology.protein ,Antibody ,030215 immunology - Abstract
The detection of HLA antibodies is important in clinical practice, such as platelet transfusion refractoriness and transfusion-related lung injury. However, difficulties are associated with the preparation of panel cells for conventional HLA detection systems using intact cells, such as the immunocomplex capture fluorescence analysis (ICFA). Based on an ICFA analysis, HEK293 cells stably transfected with the HLA-A locus were used instead of peripheral blood mononuclear cells (PBMC). The reactivity, sensitivity, and stability of transfectants were examined. All 20 antisera to HLA-A identified by LABScreen® Single Antigen class I (LS-SA1) were reactive to our modified-ICFA (m-ICFA) and showed the same specificities as those in LS-SA1, indicating the cell surface expression and correct antigenicity of the HLA-A locus in transfectants. The expression of HLA class I antigens was similar between transfectants frozen for 6 years and those prior to freezing. In the reaction of the anti-A24 or anti-A33 antibody vs each transfectant, the index of m-ICFA was higher than that of WAKFlow® ICFA. Our m-ICFA also showed that false negative reactions sometimes observed in capture assays may be avoided. By using HLA-A transfectants as ICFA targets, we herein developed m-ICFA. Our m-ICFA may avoid false negative reactions of capture assay like enzyme-linked immunosorbent assay and can also be carried out in almost any laboratory without cell culture facilities.
- Published
- 2021
26. Crossover stenting across the deep femoral artery entry: a multicenter retrospective study
- Author
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Yoshio Kobayashi, Makoto Utsunomiya, Nobuhito Kaneko, Yo Iwata, Daisuke Ueshima, Tomoyuki Umemoto, Toru Miyazaki, Tatsuki Doijiri, Teppei Murata, Kentaro Jujo, and Tetsuo Yamaguchi
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Ischemia ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Amputation, Surgical ,Peripheral Arterial Disease ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Risk Factors ,medicine ,Deep Femoral Artery ,Humans ,Radiology, Nuclear Medicine and imaging ,Registries ,030212 general & internal medicine ,Vascular Patency ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Endovascular Procedures ,Stent ,Interventional radiology ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Limb ischemia ,Surgery ,Femoral Artery ,Treatment Outcome ,Amputation ,Female ,Stents ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Crossover stenting of femoral bifurcation raises the concern of jeopardizing the deep femoral artery (DFA) entry, thereby increasing future risk of limb-threatening ischemia and amputation. This retrospective multicenter study compared clinical outcomes of crossover stenting and non-crossover stenting for ostial superficial femoral artery (SFA) lesions. We reviewed 125 limbs in 103 patients with successful stent implantation for ostial SFA lesions and allocated them to two groups, based on whether the stent crossed over the DFA orifice (CO, n = 54) or not (NC, n = 71). The decision of applying whether CO or NC was at the operators' discretion. Primary endpoints were incidences of major amputation and acute limb ischemia (ALI) at 24 months, and secondary endpoints were incidences of death, target lesion revascularization (TLR), composite of amputation or death, and major adverse limb events which was a composite of major amputation, ALI, TLR, or death at 24 months. Baseline characteristics were similar between the groups. Major amputation occurred only in the NC group, while ALI occurred only in the CO group. Kaplan-Meier estimation showed no significant differences in incidences of major amputation (NC: 3.0% vs. CO: 0.0%, p = 0.21), ALI, or any of the secondary endpoints. However, there was a trend towards higher incidence of ALI in the CO group (NC 0.0% vs. CO 3.9%, p = 0.11). Crossover stenting did not result in a significant difference in major amputation compared to non-crossover stenting within 24 months. However, it showed a trend towards higher incidence of ALI.
- Published
- 2017
27. Flow cytometric quantitation of platelet phagocytosis by monocytes using a pH-sensitive dye, pHrodo-SE
- Author
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Toshiaki Kato, Toshihiko Torigoe, Hisami Ikeda, Toru Miyazaki, Keiji Matsubayashi, Shigeru Takamoto, Mitsuhiro Fujihara, Shuichi Kino, Daisuke Takahashi, Noriyuki Sato, Hiroshi Azuma, and Shinichiro Sato
- Subjects
Blood Platelets ,Male ,0301 basic medicine ,Isoantigens ,Phagocytosis ,Lymphocyte ,Immunology ,Platelet Transfusion ,Carboxyfluorescein diacetate succinimidyl ester ,Peripheral blood mononuclear cell ,Monocytes ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,HLA Antigens ,medicine ,Humans ,Immunology and Allergy ,Platelet ,Fluorescent Dyes ,biology ,Monocyte ,Hydrogen-Ion Concentration ,Flow Cytometry ,Prognosis ,Molecular biology ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Platelet transfusion ,Blood Grouping and Crossmatching ,chemistry ,biology.protein ,Antibody ,030215 immunology - Abstract
Antibody-mediated phagocytosis of platelets using a flow cytometric monocyte-based phagocytosis assay (FMPA) has been shown to predict the outcome of platelet transfusion. The easy adherence between platelets and monocytes even in the absence of an antibody is regarded as one of limitations of the FMPA. To improve the FMPA for prediction of transfusion outcome, we used the pH-sensitive dye pHrodo succinimidyl ester (pHrodo-SE), which has weak fluorescence at neutral pH and has increased fluorescence intensity in low pH conditions such as in lysomes. Platelets stained with pHrodo-SE were sensitized with an HLA class I monoclonal antibody (w6/32 clone) or anti-HLA class I containing antisera. The platelets were incubated with monocyte-enriched mononuclear cells. Phagocytic activity was assessed by the percentage of monocytes that phagocytosed platelets. Sensitization of platelets with w6/32 significantly increased platelet phagocytosis by monocytes in dose- and time-dependent manners. Anti-HLA class I antibody-containing sera caused platelet phagocytosis in a cognate antigen-antibody-dependent manner. There was a significant correlation (r=0.69, p
- Published
- 2017
28. Effects of Smartphone Use on Behavior While Walking
- Author
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Hiroshi Tatsumi, Toru Miyazaki, Kayoko Tsutsumi, Takuya Fujiki, and Syuji Yoshiki
- Subjects
050210 logistics & transportation ,Computer science ,business.industry ,Embedded system ,0502 economics and business ,05 social sciences ,0501 psychology and cognitive sciences ,Accelerometer ,business ,050105 experimental psychology ,Simulation - Published
- 2017
29. Evaluating a Palliative Medicine Education Program for Undergraduate Medical Students at a Regional Hospice
- Author
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Eriko Yamanaka, Kumiko Matsushita, Mihoko Takahashi, Keita Watanabe, Manabu Tatokoro, and Toru Miyazaki
- Subjects
03 medical and health sciences ,0302 clinical medicine ,Nursing ,business.industry ,Medicine ,030212 general & internal medicine ,General Medicine ,030204 cardiovascular system & hematology ,business - Published
- 2017
30. Benign Intrahepatic Bile Duct Stricture Difficult to Differentiate from an Intrahepatic Cholangiocarcinoma
- Author
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Shogo Tanaka, Kazuhisa Kaneda, Toru Miyazaki, Masato Okawa, Shoji Kubo, Takatsugu Yamamoto, Koichi Ohno, and Takahiro Uenishi
- Subjects
medicine.medical_specialty ,business.industry ,Gastroenterology ,Intrahepatic bile ducts ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Surgery ,business ,Intrahepatic Cholangiocarcinoma - Published
- 2017
31. Inflammatory and anti-inflammatory states of adipose tissue in transgenic mice bearing a single TCR
- Author
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Ken Ichi Yamamura, Naoki Takeda, Kaori Taniguchi, Satoko Arai, Toru Miyazaki, and Ayaka Matsumoto
- Subjects
0301 basic medicine ,Genetically modified mouse ,obesity ,medicine.medical_specialty ,TCR transgenic mouse ,Receptors, Antigen, T-Cell, alpha-beta ,Transgene ,Adipose tissue macrophages ,T cell ,Immunology ,Adipose tissue ,chemical and pharmacologic phenomena ,Mice, Transgenic ,Inflammation ,Biology ,T-Lymphocytes, Regulatory ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Immunology and Allergy ,Macrophage ,adipose tissue inflammation ,Macrophages ,FOXP3 ,hemic and immune systems ,General Medicine ,Dietary Fats ,Editor's Choice ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Adipose Tissue ,030220 oncology & carcinogenesis ,Featured Article of the Month ,medicine.symptom - Abstract
A skewed TCR repertoire does not directly trigger inflammation in adipose tissue, Obesity is accompanied by chronic, low-grade inflammation in adipose tissue, which is associated with insulin resistance and consequent multiple metabolic diseases. In addition to M1 macrophage infiltration, multiple involvements of adipose tissue T lymphocytes in the progression of inflammation have been highlighted recently. Here, we isolated a specific Vα5/Vβ8.2 TCR-bearing T cell that accumulated in obese adipose tissue of mice, and generated transgenic mice expressing this TCR. Under lean conditions with a normal chow diet, CD4+FoxP3+ Treg cells and M2 macrophages increased in adipose tissue with ageing in wild-type mice, but not in transgenic mice. However, both mice exhibited no obvious adipose tissue inflammation such as the formation of crown-like structures (CLSs) of infiltrating macrophages. When fed a high-fat diet, the proportion of adipose tissue Treg cells was markedly small at a similar level in transgenic and wild-type mice. Both types of mice exhibited comparable inflammatory states in adipose tissue, including vast formation of macrophage CLSs, accompanied by insulin resistance. Together, our findings suggest that the absence of an increase in Treg cells and M2 macrophages is not sufficient to initiate inflammatory macrophage infiltration in lean adipose tissue and also provide a new view about the involvement of T cells in promoting obesity-associated inflammation.
- Published
- 2017
32. Homage to Mechnikov – the phagocytic system: past and present
- Author
-
Toru Miyazaki
- Subjects
0301 basic medicine ,Phagocytes ,03 medical and health sciences ,030104 developmental biology ,Famous Persons ,business.industry ,Research ,Immunology ,Humans ,Immunology and Allergy ,Medicine ,business ,Classics - Published
- 2018
33. A new antigen SUMI carried on glycophorin A encoded by the GYPA*M with c.91AC (p.Thr31Pro) belongs to the MNS blood group system
- Author
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Shoichi, Ito, Sayaka, Kaito, Toru, Miyazaki, Go, Kikuchi, Kazumi, Isa, Hatsue, Tsuneyama, Ryo, Kurita, Kenichi, Ogasawara, Makoto, Uchikawa, and Masahiro, Satake
- Subjects
Male ,Erythrocytes ,Amino Acid Substitution ,Mutation, Missense ,Humans ,MNSs Blood-Group System ,Female ,Glycophorins - Abstract
MNS is one of the highly polymorphic blood groups comprising many antigens generated by genomic recombination among the GYPA, GYPB, and GYPE genes as well as by single-nucleotide changes. We report a patient with red blood cell (RBC) antibody against an unknown low-frequency antigen, tentatively named SUMI, and investigated its carrier molecule and causal gene.Standard serologic tests, including enzyme tests, were performed. Monoclonal anti-SUMI-producing cells (HIRO-305) were established by transformation and hybridization methods using lymphocytes from a donor having anti-SUMI. SUMI+ RBCs were examined by immunocomplex capture fluorescence analysis (ICFA) using HIRO-305 and murine monoclonal antibodies against RBC membrane proteins carrying blood group antigens. Genomic DNA was extracted from whole blood, and the GYPA gene was analyzed by polymerase chain reactions and Sanger sequencing.Serologic screening revealed that 23 of the 541,522 individuals (0.0042%) were SUMI+, whereas 1351 of the 10,392 individuals (13.0%) had alloanti-SUMI. SUMI antigen was sensitive to ficin, trypsin, pronase, and neuraminidase, but resistant to α-chymotrypsin and sulfydryl-reducing agents. ICFA revealed that the SUMI antigen was carried on glycophorin A (GPA). According to Sanger sequencing and cloning, the SUMI+ individuals had a GYPA*M allele with c.91AC (p.Thr31Pro), which may abolish the O-glycan attachment site.The new low-frequency antigen SUMI is carried on GPA encoded by the GYPA*M allele with c.91AC (p.Thr31Pro). Neuraminidase sensitivity suggests that glycophorin around Pro31 are involved in the SUMI determinant.
- Published
- 2019
34. Outcomes of Non-B Non-C Hepatocellular Carcinoma with Reference to Patients with Interferon-Induced Hepatitis C Virus Eradication
- Author
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Shogo Tanaka, Toru Miyazaki, Shigekazu Takemura, Shoji Kubo, Hiroji Shinkawa, Tokuji Ito, and Takanori Aota
- Subjects
medicine.medical_specialty ,Multivariate analysis ,Carcinoma, Hepatocellular ,Hepatitis C virus ,Alcoholic hepatitis ,Hepacivirus ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Sobriety ,Interferon ,Internal medicine ,medicine ,Humans ,neoplasms ,Retrospective Studies ,business.industry ,Hazard ratio ,Liver Neoplasms ,medicine.disease ,Prognosis ,Hepatitis C ,digestive system diseases ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Surgery ,Liver function ,Interferons ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
This study aimed to evaluate survival outcomes in patients with non-B non-C hepatocellular carcinoma (NBNC-HCC) with reference to patients with HCC achieving sustained virological response (SVR) by preoperative interferon (IFN) treatment for chronic hepatitis C. We examined 781 patients who underwent hepatic resection for HCC. They were classified into NBNC-HCC, SVR-HCC, and non-SVR HCC groups. Multivariate analysis for recurrence-free survival (RFS) and overall survival (OS) revealed that the adjusted hazard ratios (HR) of NBNC-HCC and non-SVR HCC groups with reference to the SVR-HCC group were 1.46 (p = 0.10) and 2.10 (p
- Published
- 2019
35. AIM-deficient mouse fed a high-trans fat, high-cholesterol diet: a new animal model for nonalcoholic fatty liver disease
- Author
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Satoko Arai, Toru Miyazaki, Yuki Ishida, Mai Sasaki, Toru Nonomura, and Ginga Komatsu
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Trans fat ,obesity ,Original ,Diet, High-Fat ,General Biochemistry, Genetics and Molecular Biology ,High cholesterol ,Pathogenesis ,03 medical and health sciences ,Mice ,hepatocellular carcinoma (HCC) ,0302 clinical medicine ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Receptors, Immunologic ,apoptosis inhibitor of macrophage (AIM) ,nonalcoholic fatty liver disease (NAFLD) ,Receptors, Scavenger ,General Veterinary ,business.industry ,D09100301 high-trans fat high-cholesterol diet ,General Medicine ,Trans Fatty Acids ,medicine.disease ,Obesity ,digestive system diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Cholesterol ,Hepatocellular carcinoma ,Animal Science and Zoology ,Female ,Steatosis ,business ,Apoptosis Regulatory Proteins ,030217 neurology & neurosurgery - Abstract
Owing to changes in lifestyle, nonalcoholic fatty liver disease (NAFLD) is becoming a common form of chronic liver injury. NAFLD comprises a wide variety of disease stages, from simple steatosis to nonalcoholic steatohepatitis, which is a risk factor for the development of hepatocellular carcinoma (HCC). Because animal models for NAFLD are needed to investigate the precise pathogenesis, we aimed to establish a new mouse model employing mice deficient for apoptosis inhibitor of macrophage (AIM-/-), which exhibit accelerated lipid storage in the liver and high susceptibility to developing HCC in response to a high-fat diet (HFD). AIM-/- mice were fed the D09100301 diet, which contains 40 kcal% fat (trans fat 30 kcal%), high cholesterol (2%), and 40 kcal% carbohydrates (20 kcal% fructose), and then features of obesity and NAFLD including steatosis, inflammation, fibrosis, and HCC development were analyzed. Although a comparable grade of liver steatosis was promoted in AIM-/- mice by the D09100301 diet and the standard HFD (60 kcal% largely lard fat), significantly less lipid storage in visceral fat was observed when the mice were fed the D09100301 diet. Accelerated liver inflammation was promoted by the D09100301 diet compared with the HFD, but interestingly, HCC development was decreased in mice fed the D09100301 diet. Our findings suggest that AIM-/- mice fed the D09100301 diet exhibited a phenotype that resembled nonobese NAFLD patients and thus could be an appropriate tool to study the pathophysiology by which obesity increases the risk of HCC.
- Published
- 2018
36. Association of apoptosis inhibitor of macrophage (AIM) expression with urinary protein and kidney dysfunction
- Author
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Satoko Arai, Eri Umeda, Akihiro Sagara, Norihiko Sakai, Akinori Hara, Megumi Oshima, Toru Miyazaki, Yasuyuki Shinozaki, Shuichi Kaneko, Miho Shimizu, Kengo Furuichi, Shinji Kitajima, Tadashi Toyama, Takashi Wada, and Yasunori Iwata
- Subjects
Adult ,Male ,0301 basic medicine ,Nephrology ,medicine.medical_specialty ,Pathology ,Physiology ,Biopsy ,Kidney Glomerulus ,Renal function ,Inflammation ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Receptors, Scavenger ,Kidney ,Creatinine ,biology ,urogenital system ,business.industry ,Macrophages ,Endothelial Cells ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Proteinuria ,030104 developmental biology ,medicine.anatomical_structure ,Immunoglobulin M ,chemistry ,Multivariate Analysis ,biology.protein ,Female ,Kidney Diseases ,medicine.symptom ,Apoptosis Regulatory Proteins ,business ,Glomerular Filtration Rate ,Kidney disease - Abstract
Apoptosis inhibitor of macrophage (AIM) expressed on macrophages prolongs inflammation by protecting macrophages from apoptosis. Most circulating AIM co-exists with immunoglobulin M (IgM). AIM’s pathophysiological role in relation to IgM remains unclear. Here we evaluated the glomerular expression/deposition of AIM and IgM in the kidney using immunohistochemistry and its associations with clinical manifestations in 43 patients with biopsy-confirmed kidney diseases. Kidney biopsy tissue from all patients was immunostained for AIM and IgM. Staining patterns and percent stained areas within the glomeruli were determined. Cells expressing AIM were identified by co-staining with macrophage and endothelial cell surface markers. Correlations between staining results and clinical parameters were evaluated using univariate and multivariate analyses. AIM was deposited in various areas, such as mesangial and capillary area. A part of AIM expression was localized to CD68-positive macrophages in the glomerulus. Amount of glomerular expression was positively correlated with urinary protein in patients with severe proteinuria (urinary protein ≥0.5 g/day) and kidney dysfunction [estimated glomerular filtration ratio (eGFR)
- Published
- 2016
37. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice
- Author
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Tomoko Takano, Akira Nishiyama, Eisei Noiri, Shunsuke Kusunoki, Toru Miyazaki, Natsumi Maehara, Yusuke Suzuki, Yasunori Yoshihara, Naoki Yahagi, Tomoko Yamazaki, Ayaka Matsumoto, Ryoichi Sugisawa, Yoji Tsugawa, Mayumi Mori, Kent Doi, Lakshman Gunaratnam, Ryosuke Takai, Kento Kitada, Satoko Arai, Akiko Takahata, and Xizhong Zhang
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Necrosis ,Apoptosis Inhibitor ,Enzyme-Linked Immunosorbent Assay ,Biology ,Kidney ,Real-Time Polymerase Chain Reaction ,urologic and male genital diseases ,General Biochemistry, Genetics and Molecular Biology ,Kidney Tubules, Proximal ,Mice ,03 medical and health sciences ,Phagocytosis ,In Situ Nick-End Labeling ,medicine ,Animals ,Humans ,Macrophage ,Hepatitis A Virus Cellular Receptor 1 ,Receptors, Immunologic ,Aged ,Aged, 80 and over ,Mice, Knockout ,Receptors, Scavenger ,urogenital system ,Macrophages ,Acute kidney injury ,Membrane Proteins ,Kidney metabolism ,General Medicine ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Immunohistochemistry ,HEK293 Cells ,030104 developmental biology ,medicine.anatomical_structure ,Renal pathology ,Reperfusion Injury ,Female ,medicine.symptom ,Apoptosis Regulatory Proteins ,Kidney disease - Abstract
Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.
- Published
- 2016
38. The IgM pentamer is an asymmetric pentagon with an open groove that binds the AIM protein
- Author
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Toru Miyazaki, Satoko Arai, Masahide Kikkawa, Akihisa Tsutsumi, Shigeru Matsuoka, Emiri Hiramoto, and Risa Suzuki
- Subjects
Receptors, Scavenger ,0301 basic medicine ,Multidisciplinary ,Protein Conformation ,Chemistry ,Pentamer ,Stereochemistry ,Cell Membrane ,Disulfide bond ,SciAdv r-articles ,Biochemistry ,J chain ,03 medical and health sciences ,030104 developmental biology ,Protein structure ,Immunoglobulin M ,Soluble Immunoglobulin ,Animals ,Molecule ,Receptors, Immunologic ,Apoptosis Regulatory Proteins ,Groove (joinery) ,Research Articles ,Research Article - Abstract
We demonstrate the bona fide 2D structure of the IgM pentamer and its association with AIM protein., Soluble immunoglobulin M (IgM) forms a pentamer containing a joining (J) chain polypeptide. While IgM pentamer has various immune functions, it also behaves as a carrier of circulating apoptosis inhibitor of macrophage (AIM; also called CD5L) protein that facilitates repair during different diseases. AIM binds to the IgM pentamer solely in the presence of the J chain. Here, using a single-particle negative-stain electron microscopy, we found that the IgM pentamer exhibits an asymmetric pentagon containing one large gap, which is markedly different from the textbook symmetric pentagon model. A single AIM molecule specifically fits into the gap, cross-bridging two IgM-Fc that form the edges of the gap through a disulfide bond at one side and a charge-based interaction at the other side. The discovery of the bona fide shape of the IgM pentamer advances our structural understanding of the pentameric IgM and its binding mode with AIM.
- Published
- 2018
39. Impact of chronic kidney disease on long-term clinical outcomes of everolimus-eluting stent implantation: A subanalysis of the Tokyo-MD PCI registry
- Author
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Ken Kurihara, Mitsutoshi Asano, Taro Sasaoka, Toru Miyazaki, Shunji Yoshikawa, Takashi Ashikaga, Mitsuaki Isobe, and Tokyo-MD Pci Study Investigators
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Comorbidity ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Kidney ,03 medical and health sciences ,0302 clinical medicine ,Percutaneous Coronary Intervention ,Interquartile range ,Risk Factors ,Internal medicine ,Cause of Death ,medicine ,Prevalence ,Humans ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,Myocardial infarction ,Everolimus ,Registries ,Renal Insufficiency, Chronic ,Tokyo ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Coronary Thrombosis ,Incidence ,Hazard ratio ,Stent ,Cardiovascular Agents ,Drug-Eluting Stents ,General Medicine ,Middle Aged ,medicine.disease ,Treatment Outcome ,Conventional PCI ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Mace ,Kidney disease ,Glomerular Filtration Rate - Abstract
OBJECTIVE The aim of the study was to investigate the impact of chronic kidney disease (CKD) on the 5-year clinical outcomes of everolimus-eluting stent (EES) implantation. BACKGROUND Recent studies have demonstrated the safety and efficacy of EES. However, limited information exists on the long-term clinical outcomes associated with CKD. METHODS The Tokyo-MD PCI study is a multi-center observational study designed to describe the clinical outcomes of unselected patients after EES implantation. In this subanalysis, patients on maintenance hemodialysis were excluded, and patients with (n = 316) or without (n = 1,424) CKD were evaluated for their 5-year incidence rates of major adverse cardiac events (MACEs), defined as death, non-fatal myocardial infarction, ischemia driven target lesion revascularization (ID-TLR), and stent thrombosis (ST). RESULTS The mean and median follow-up duration were 1,391 ± 557 days and 1,769 days (interquartile range, 1,012-1,800 days), respectively. Although the incidence of ID-TLR and ST was similar between patients with and without CKD (4.9% vs. 3.7%, P = 0.26, 0.5% vs. 1.0%, P = 0.20, respectively), cardiac death and MACE were significantly higher in patients with CKD than in those without CKD (6.5% vs. 2.9%, P = 0.007, 26.9% vs. 14.0%, P
- Published
- 2018
40. Feasibility and safety of uninterrupted apixaban in patients undergoing radiofrequency ablation for atrial fibrillation
- Author
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Toru Miyazaki, Kenzo Hirao, Kenichiro Otomo, Kentaro Goto, Yuichi Ono, Asami Suzuki, Susumu Tao, Ken Kurihara, and Yuki Osaka
- Subjects
Male ,medicine.medical_specialty ,Radiofrequency ablation ,Pyridones ,medicine.medical_treatment ,Catheter ablation ,030204 cardiovascular system & hematology ,law.invention ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,law ,Physiology (medical) ,Atrial Fibrillation ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,business.industry ,Cerebral infarction ,Warfarin ,Infant, Newborn ,Anticoagulants ,Atrial fibrillation ,medicine.disease ,Ablation ,Surgery ,Treatment Outcome ,Catheter Ablation ,Feasibility Studies ,Pyrazoles ,Apixaban ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,Cohort study - Abstract
An optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during atrial fibrillation (AF) ablation. Limited data are available on the uninterrupted use of apixaban in patients with AF undergoing catheter ablation. This study aimed to evaluate the safety and efficacy of uninterrupted apixaban in patients undergoing radiofrequency ablation for AF. In particular, we evaluated silent cerebral infarction (CI) during radiofrequency catheter ablation of AF. This was a prospective and nonrandomized cohort study. A total of 259 consecutive patients who underwent AF ablation were evaluated; 157 patients received apixaban (Api group), and 102 patients received dose-adjusted (PT-INR 2.0-3.0) warfarin (Wf group). All oral anticoagulants were continued throughout the periprocedural period, including the morning of the procedure. Intravenous heparin was administered during the procedure and neutralized by protamine at the end of the procedure. Sixty-one patients underwent magnetic resonance imaging (MRI) after the procedure to evaluate for silent CI. Mean age was 66 ± 11 years; there were 91 men (73.7%) and 148 cases of paroxysmal AF (57.1%). No symptomatic CI was observed. Silent CI occurred in 6/61 patients (9.8%). No significant difference was observed between the Api group (4/30 patients, 13.3%) and the Wf group (2/31 patients, 6.5%). There was no significant difference regarding major bleeding events between the Api group (1/157 patients, 0.6%) and the Wf group (2/102 patients, 2.0%). The safety and efficacy of uninterrupted apixaban for patients undergoing AF ablation were equivalent to warfarin for preventing bleeding and thromboembolic complications.
- Published
- 2018
41. Independent modes of disease repair by AIM protein distinguished in AIM-felinized mice
- Author
-
Ryoichi Sugisawa, Satoko Arai, Toru Miyazaki, Emiri Hiramoto, Naoki Takeda, Ken Ichi Yamamura, and Ginga Komatsu
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Kupffer Cells ,Transgene ,lcsh:Medicine ,Mice, Transgenic ,Diet, High-Fat ,Article ,03 medical and health sciences ,Mice ,Internal medicine ,medicine ,Adipocytes ,Macrophage ,Animals ,Obesity ,Transgenes ,Receptors, Immunologic ,lcsh:Science ,Receptor ,Disease Resistance ,Multidisciplinary ,biology ,business.industry ,lcsh:R ,Fatty liver ,Liver Neoplasms ,Acute kidney injury ,medicine.disease ,Fatty Liver ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Immunoglobulin M ,Hepatocellular carcinoma ,biology.protein ,Cats ,Hepatocytes ,lcsh:Q ,Signal transduction ,business ,Apoptosis Regulatory Proteins ,Protein Binding ,Signal Transduction - Abstract
Tissue macrophage-derived apoptosis inhibitor of macrophage (AIM, encoded by cd5l gene) is a circulating protein that has suppressive functions in a broad range of diseases including obesity, liver steatosis, hepatocellular carcinoma (HCC), and acute kidney injury (AKI). In healthy states, high levels of AIM circulate in the inactivated state by associating with the immunoglobulin M (IgM) pentamer in the blood, whereas during AKI, AIM dissociates from IgM and gains disease repair activity. Here, we assessed whether AIM activation via its release from IgM is required to ameliorate other diseases. To this end, we employed a mouse line in which mouse AIM was replaced with feline AIM (AIM-felinized mice). Because feline AIM rarely dissociates from IgM due to its extremely high binding affinity for IgM, these mice exhibited deficient AKI repair as in cats. When fed a high-fat diet (HFD), similar to AIM-deficient (AIM−/−) mice, AIM-felinized mice exhibited enhanced triacylglycerol deposition in visceral adipocytes and hepatocytes, resulting in more prominent obesity and fatty liver than in wild-type mice. In contrast, the incidence of HCC after a 1-year HFD was remarkably lower in AIM-felinized mice than in AIM−/− mice, suggesting that AIM produced by liver Kupffer macrophages might directly facilitate the elimination of HCC cells. Accordingly, the marked deposition of AIM accompanied by accumulation of Kupffer cells was obvious during HCC tumour development in AIM-felinized mice. Δsµ mice, which harbour almost no circulating AIM due to the lack of secreted IgM, showed a phenotype comparable with that of AIM-felinized mice in prevention of those diseases. Thus, blood AIM released from IgM contributes to suppression of obesity and fatty liver as in AKI, whereas macrophage-derived noncirculating AIM mainly prevents HCC development. Our study depicted two different modes of disease prevention/repair facilitated by AIM, which could be the basis for HCC therapy that works by increasing AIM expression in macrophages.
- Published
- 2018
42. Corrigendum to 'Flow cytometric quantitation of platelet phagocytosis by monocytes using a pH-sensitive dye, pHrodo-SE' [Journal of Immunological Methods 447 (2017) 57-64]
- Author
-
Hiroshi Azuma, Toru Miyazaki, Toshiaki Kato, Shuichi Kino, Toshihiko Torigoe, Noriyuki Sato, Mitsuhiro Fujihara, Shinichiro Sato, Daisuke Takahashi, Keiji Matsubayashi, Shigeru Takamoto, and Hisami Ikeda
- Subjects
biology ,Lymphocyte ,Phagocytosis ,Monocyte ,Immunology ,030204 cardiovascular system & hematology ,Carboxyfluorescein diacetate succinimidyl ester ,Peripheral blood mononuclear cell ,Molecular biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine.anatomical_structure ,Platelet transfusion ,chemistry ,medicine ,biology.protein ,Immunology and Allergy ,Platelet ,Antibody ,030215 immunology - Abstract
Antibody-mediated phagocytosis of platelets using a flow cytometric monocyte-based phagocytosis assay (FMPA) has been shown to predict the outcome of platelet transfusion. The easy adherence between platelets and monocytes even in the absence of an antibody is regarded as one of limitations of the FMPA. To improve the FMPA for prediction of transfusion outcome, we used the pH-sensitive dye pHrodo succinimidyl ester (pHrodo-SE), which has weak fluorescence at neutral pH and has increased fluorescence intensity in low pH conditions such as in lysomes. Platelets stained with pHrodo-SE were sensitized with an HLA class I monoclonal antibody (w6/32 clone) or anti-HLA class I containing antisera. The platelets were incubated with monocyte-enriched mononuclear cells. Phagocytic activity was assessed by the percentage of monocytes that phagocytosed platelets. Sensitization of platelets with w6/32 significantly increased platelet phagocytosis by monocytes in dose- and time-dependent manners. Anti-HLA class I antibody-containing sera caused platelet phagocytosis in a cognate antigen-antibody-dependent manner. There was a significant correlation (r=0.69, p
- Published
- 2018
43. Obesity and recurrence-free survival in patients with hepatocellular carcinoma after achieving sustained virological response to interferon therapy for chronic hepatitis C
- Author
-
Takatsugu Yamamoto, Shogo Tanaka, Shigekazu Takemura, Tokuji Ito, Shoji Kubo, Takanori Aota, Masaki Koda, Hiroji Shinkawa, and Toru Miyazaki
- Subjects
medicine.medical_specialty ,obesity ,Multivariate analysis ,recurrence ,Milan criteria ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Survival rate ,Univariate analysis ,business.industry ,Hazard ratio ,Original Articles ,hepatocellular carcinoma ,medicine.disease ,Obesity ,Confidence interval ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Surgery ,Original Article ,interferon therapy ,sustained virological response ,business - Abstract
Aim Some patients who achieve a sustained virological response (SVR) to interferon (IFN) treatment for chronic hepatitis C prior to hepatic resection for hepatocellular carcinoma (HCC) experience postoperative recurrence. This study investigated the relationship between obesity and postoperative HCC recurrence in SVR patients. Methods Fifty‐nine patients who had achieved SVR before hepatic resection were evaluated. Patients had a solitary tumor ≤5 cm in diameter or ≤3 lesions each ≤3 cm in size with no macroscopic vascular invasion (Milan criteria). Patient characteristics potentially associated with recurrence risk were investigated. Results Three‐, 5‐, and 7‐year recurrence‐free survival after surgery were 65%, 44%, and 41%, respectively. Univariate analysis showed that obesity (P < .01), hypertension (P = .038), and non‐anatomical resection (P = .022) were significantly associated with a lower recurrence‐free survival rate. In a multivariate analysis, obesity (hazard ratio, 2.8; 95% confidence interval [CI] 1.3‐6.1; P < .01) and non‐anatomical resection (hazard ratio, 2.7; 95% CI 1.1‐6.2; P = .025) were independently associated with postoperative recurrence. Three‐, 5‐, and 7‐year overall survival rates after surgery were 100%, 80%, and 64% in obese patients and 100%, 92%, and 82% in non‐obese patients, respectively (P = .014). However, other variables showed no significant difference in the overall survival rate. Conclusions Obesity and non‐anatomical resection were independent risk factors for HCC recurrence after hepatic resection and successful IFN therapy. Obesity is an important clinical problem to consider to improve postoperative outcomes in such patients.
- Published
- 2018
44. Diagnostic and Therapeutic Values of Apoptosis Inhibitor of Macrophage in Nash-Associated Hepatocellular Carcinoma
- Author
-
Noriyuki Koyama, Takeshi Okanoue, Tomoko Yamazaki, and Toru Miyazaki
- Subjects
Apoptosis Inhibitor ,business.industry ,nutritional and metabolic diseases ,Diagnostic tools ,medicine.disease ,digestive system ,digestive system diseases ,Hepatocellular carcinoma ,Carcinoma ,Cancer research ,Medicine ,Biomarker (medicine) ,Macrophage ,Steatohepatitis ,business ,neoplasms - Abstract
The number of patients in Non-alcoholic Steatohepatitis (NASH) and its associated Hepato Cellular Carcinoma (HCC) is increasing rapidly along with the change of lifestyle. So far, however, no diagnostic tools specifically use for NASH-associated HCC have not been established yet. Recently, we have reported circulating levels of activated Apoptosis Inhibitor of Macrophage (AIM, also called CD5L) can be a sensitive and specific biomarker to diagnose NASH-associated HCC in human. In addition, we demonstrated that AIM facilitated the diminishment of HCC tumors in mice. In this report, we discuss about the benefits of application of AIM as future diagnostic and therapeutic tools against NASH-associated HCC.
- Published
- 2018
45. A defense system against multiple diseases via biological garbage clearance mediated by soluble scavenger proteins
- Author
-
Toru Miyazaki and Satoko Arai
- Subjects
Biochemistry ,Phagocytosis ,Immunology ,Immunology and Allergy ,Biology ,Garbage ,Scavenger (chemistry) ,Microbiology - Published
- 2015
46. Analysis of steering wheel operations based on human arm mechanical properties
- Author
-
Kazuo NISHIKAWA, Kouji FURUKAWA, Isao KAWATE, Toru MIYAZAKI, Takahide NOUZAWA, and Toshio TSUJI
- Published
- 2015
47. Activation of apoptosis inhibitor of macrophage is a sensitive diagnostic marker for NASH-associated hepatocellular carcinoma
- Author
-
Satoko Arai, Hirota Jiro, Yasuhide Mitsumoto, Toru Miyazaki, Toshihide Shima, Yoshihiro Kanbara, Kanetsuki Yuka, Masayuki Mizuno, Asai Tomohide, Tomoko Yamazaki, Noriyuki Koyama, and Takeshi Okanoue
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Pathology ,Carcinoma, Hepatocellular ,Apoptosis Inhibitor ,Biopsy ,digestive system ,Gastroenterology ,Severity of Illness Index ,03 medical and health sciences ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Biomarkers, Tumor ,Macrophage ,Humans ,Stage (cooking) ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Receptors, Scavenger ,Receiver operating characteristic ,medicine.diagnostic_test ,business.industry ,Fatty liver ,Liver Neoplasms ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Immunoglobulin M ,Liver ,ROC Curve ,Hepatocellular carcinoma ,Liver biopsy ,Female ,Steatohepatitis ,business ,Apoptosis Regulatory Proteins - Abstract
A diagnostic marker is needed enabling early and specific diagnosis of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH). Our recent findings have indicated that circulating apoptosis inhibitor of macrophage (AIM), which usually associates with IgM pentamer in the blood, is activated by its dissociation from IgM. We investigated the serum levels of IgM-free AIM for AIM activation and its possible relationship with development of HCC in NASH. Serum levels of IgM-associated and IgM-free AIM were evaluated in patients with non-alcoholic fatty liver, NASH, and NASH-HCC using enzyme-linked immunosorbent assays and immunoblots. Liver biopsy specimens were graded and staged using Brunt’s classification. Forty-two patients with fatty liver, 141 with NASH, and 26 with NASH-HCC were evaluated. Patients with stage 4 or grade 3 NASH (with or without HCC) exhibited significantly higher levels of both IgM-free and total AIM than those with fatty liver, whereas the ratio of IgM-free-to-total AIM was equivalent in these groups. Among patients with the same fibrosis stage of NASH, those with HCC had significantly higher IgM-free but not total AIM levels, resulting in a proportional increase in the IgM-free/total AIM ratio. Analysis of the areas under the receiver operating characteristic curves indicated the high sensitivity of the IgM-free AIM for NASH-HCC. Our observations suggest the activation of AIM in blood in the presence of NASH-HCC, with a significant increase in IgM-free AIM levels. IgM-free AIM serum levels appear to be a sensitive diagnostic marker for NASH-HCC.
- Published
- 2017
48. DETECTION OF ANTI-HUMAN PLASMA PROTEINS USING A LUMINEX SYSTEM
- Author
-
Shigeru Takamoto, Toru Miyazaki, Toshiaki Kato, Syuichi Kino, Shinichiro Sato, Keiji Matsubayashi, and Hisami Ikeda
- Subjects
business.industry ,Human plasma ,Medicine ,business ,Molecular biology - Published
- 2014
49. A Resected Case of the Pancreatic Tail Cancer with Obstruction of the Large Intestine
- Author
-
Kazunori Ohata, Takahiro Uenishi, Toru Miyazaki, Yukiko Kurashima, Chie Watanabe, Masato Okawa, Shogo Tanaka, Koichi Ohno, Takatsugu Yamamoto, and Shoji Kubo
- Published
- 2014
50. Molecular Cloning and Gene Expression of Canine Apoptosis Inhibitor of Macrophage
- Author
-
Satoko Arai, Masato Kobayashi, Shintaro Tomura, Mona Uchida, Satoshi Tamahara, Makoto Bonkobara, Tomohiro Yonezawa, Naoaki Matsuki, and Toru Miyazaki
- Subjects
DNA, Complementary ,Apoptosis Inhibitor ,scavenger receptor cysteine-rich (SRCR) superfamily ,Molecular Sequence Data ,Sequence Homology ,canine ,Spleen ,Biology ,CD5L ,Dogs ,Complementary DNA ,Canine Histiocytic Sarcoma ,Gene expression ,Internal Medicine ,medicine ,Animals ,Amino Acid Sequence ,Cloning, Molecular ,apoptosis inhibitor of macrophage (AIM) ,Receptor ,Lung ,DNA Primers ,Receptors, Scavenger ,Base Sequence ,General Veterinary ,Gene Expression Profiling ,Sequence Analysis, DNA ,Note ,Molecular biology ,Gene expression profiling ,medicine.anatomical_structure ,Liver ,Cell culture ,Lymph Nodes ,CD36 ,Sequence Alignment - Abstract
Apoptosis inhibitor of macrophage (AIM) plays roles in survival of macrophages. In this study, we cloned canine AIM cDNA and observed its transcriptional expression levels in various tissues. The coding sequence of canine AIM was 1,023 bp encoding 340 amino acid residues, which had around 65% homology with those of the human, mouse and rat. Transcriptional expression of AIM was observed in the spleen, lung, liver and lymph node, which confirmed the expression of canine AIM in tissue macrophages. Moreover, AIM was highly expressed in one of the canine histiocytic sarcoma cell lines. CD36, the receptor of AIM, was also expressed in various tissues and these cell lines. These findings are useful to reveal the actual functions of canine AIM.
- Published
- 2014
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