Details of a Researcher - Azegami, Tatsuhiko

Immunotherapy for obesity

Azegami T., Itoh H., Therapeutic Vaccines as Novel Immunotherapy: Biological and Clinical Concepts, 2020.01

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Obesity prevalence continues to increase in both adults and children worldwide and greatly contributes to increased morbidity and mortality. Although there are some anti-obesity drugs globally available for clinical use, their inadequate effectiveness coupled with safety concerns sometimes discourage the widespread use of anti-obesity medication. Because of its prolonged therapeutic effect and low frequency of administration, a therapeutic vaccine may be an attractive strategy for the prevention and treatment of obesity. Over the last two decades, several attempts have been made to develop vaccines for the control of obesity. Animal studies have shown that vaccines targeting ghrelin, glucose-dependent insulinotropic polypeptide, adipocytes, somatostatin, and adenovirus 36 successfully led to a reduction in weight gain without serious adverse effects. This chapter provides an overview of recent progress toward a therapeutic vaccine against obesity.
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Mucosal Vaccines: Innovation for Preventing Infectious Diseases, 2nd edition.

Elsevier, 2020

Scope: Plant-Based Mucosal Vaccine Delivery System, Contact page： 357-370
Plant-based mucosal vaccine delivery systems

Azegami T., Yuki Y., Kiyono H., Mucosal Vaccines: Innovation for Preventing Infectious Diseases, 2019.01

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Plant-based vaccines (PbVs), developed with novel plant genetic engineering technologies, offer a new strategy for the production, storage, and delivery of vaccines. PbVs can overcome practical and economic concerns surrounding injectable vaccines, including the need for medical staff to perform the injections and the costs of production and refrigeration. The development of unrefrigerated, needle-free vaccines will support the prevention of infectious diseases in developing countries. Although no PbV has yet been licensed for human clinical use, some are now in clinical trials. Antigen-encoding genes introduced into potatoes, lettuce, spinach, corn, tobacco, soybeans, and rice can produce vaccines against mucosal and systemic infectious diseases, including enterotoxigenic Escherichia coli, Vibrio cholerae, norovirus, influenza virus, hepatitis B virus, and rabies virus. This chapter introduces the plant genetic engineering technologies used and clinical trials of PbVs.
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Therapeutic Vaccines as Novel Immunotherapy

Springer, 2019

Scope: Immunotherapy for Obeisty, Contact page： 33-44
腎生検病理アトラス改訂版（尿細管・間質・血管病変の分類）

AZEGAMI Tatsuhiko, 2017.08

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Vaccination against connective tissue growth factor attenuates the development of renal fibrosis

Nakayama T., Azegami T., Hayashi K., Hishikawa A., Yoshimoto N., Nakamichi R., Sugita E., Itoh H.

Scientific Reports （Scientific Reports) 12 （ 1 ） 10933 2022.12

ISSN 2045-2322

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There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.
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Serum thymus and activation-regulated chemokine level is associated with the severity of chronic kidney disease-associated pruritus in patients undergoing peritoneal dialysis

Nakayama T., Morimoto K., Uchiyama K., Kusahana E., Washida N., Azegami T., Kanda T., Yoshida T., Itoh H.

Peritoneal Dialysis International （Peritoneal Dialysis International) 42 （ 4 ） 415 - 424 2022.07

ISSN 08968608

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Background: Thymus and activation-regulated chemokine (TARC), which induces a Th2-dominated inflammation, is a well-known biomarker that reflects the severity of atopic dermatitis. The present study aimed to evaluate TARC as a Th2-associated marker with chronic kidney disease-associated pruritus (CKD-aP) in patients with peritoneal dialysis (PD). Methods: This single-centre cross-sectional study included patients who underwent PD in our hospital between August 2020 and July 2021. The severity and impaired quality of life (QOL) of CKD-aP were assessed using the visual analogue scale (VAS) and Japanese version of the 5-D itch scale (5D-J), respectively. Results: A total of 48 patients with PD were included in the present study. Age and dialysis vintage were (mean ± SD) 64.8 ± 12.0 year and (median (IQR)) 38.5 (11.5–91.5) month, respectively. VAS and 5D-J scores were 3.3 ± 2.0 and 10.5 (9.0–12.0), respectively. Serum TARC level was 481.5 (278.9–603.4) pg/mL (upper limits of normal 450 pg/mL) and significantly correlated with VAS (r = 0.39, p = 0.006) and 5D-J score (r = 0.37, p = 0.009). Multivariate linear analysis revealed that higher serum TARC level was significantly associated with VAS (p < 0.001) and 5D-J score (p < 0.001). Furthermore, the serum brain natriuretic peptide level tended to be associated with VAS (p = 0.060) and 5D-J score (p = 0.029). Conclusion: Serum TARC level is an independent predictor of the severity and impaired QOL of CKD-aP in patients with PD, and TARC might be involved in the pathogenesis of CKD-aP.
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Late Dialysis Modality Education Could Negatively Predict Peritoneal Dialysis Selection

Nakayama Takashin, Nishioka Ken, Uchiyama Kiyotaka, Morimoto Kohkichi, Kusahana Ei, Washida Naoki, Yamaguchi Shintaro, Azegami Tatsuhiko, Yoshida Tadashi, Itoh Hiroshi

JOURNAL OF CLINICAL MEDICINE 11 （ 14 ） 2022.07
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Effects of renin-angiotensin system inhibitors on the incidence of unplanned dialysis

Nakayama T., Morimoto K., Uchiyama K., Kusahana E., Washida N., Azegami T., Kanda T., Yoshida T., Itoh H.

Hypertension Research （Hypertension Research) 45 （ 6 ） 1018 - 1027 2022.06

ISSN 09169636

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Unplanned dialysis initiation is associated with poor outcomes. It is controversial whether patients with advanced chronic kidney disease (CKD) should receive renin-angiotensin system (RAS) inhibitor therapy. The aim of this study was to evaluate the effect of RAS inhibitor therapy in patients with advanced CKD on the incidence of unplanned dialysis initiation. This single-center, retrospective study included patients who started maintenance dialysis at our hospital between April 2014 and March 2021. Patients who initiated dialysis within 6 months of nephrology referral or after kidney transplant were excluded. Among 334 patients (aged 70.0 [59.0–79.0] years; 28.4% women), 186 (55.7%) and 148 (44.3%) had planned and unplanned dialysis initiation, respectively. Multivariate logistic regression analysis revealed that the use of RAS inhibitors was significantly associated with a lower incidence of unplanned dialysis initiation (odds ratio [OR], 0.36; P < 0.01). Female sex (OR, 0.41; P < 0.05), use of potassium binders (OR, 0.28; P < 0.001), earlier referral to nephrology (OR, 0.39; P < 0.01), and earlier discussion of renal replacement therapy (OR, 0.33; P < 0.001) were also significantly associated with a lower incidence, whereas older age (OR, 1.28; P < 0.05), higher Charlson Comorbidity Index (OR, 1.24; P < 0.05), and faster decline in kidney function (OR, 1.29; P < 0.01) were associated with a higher risk of unplanned dialysis initiation. RAS inhibitor therapy in patients with advanced CKD is associated with a lower risk of unplanned dialysis initiation.
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Fibronectin Glomerulopathy Confused with Glomerular Endothelial Injury in a Patient with Takotsubo Cardiomyopathy

Azegami T., Hashiguchi A., Nakayama T., Hayashi K., Kanda T., Itoh H.

Internal Medicine （Internal Medicine) 61 （ 13 ） 2027 - 2032 2022

ISSN 09182918

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A 46-year-old woman developed takotsubo cardiomyopathy and nephrotic syndrome. The first kidney biopsy suggested non-immune-complex-mediated membranoproliferative glomerulonephritis (MPGN), and she was diagnosed with glomerular endothelial injury associated with takotsubo cardiomyopathy. A second biopsy was performed two years later because of persistent proteinuria despite renin-angiotensin system inhibition. This biopsy indicated non-immune-complex-mediated MPGN, but a mesangial and subendothelial substance of a higher electron density than that in the first biopsy was detected, suggesting the possibility of glomerular disease with non-immune deposits rather than endothelial injury. Finally, she was diagnosed with fibronectin nephropathy. Although rare, fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Adolescent blood pressure study using health checkup data

Azegami, Tatsuhiko

学事振興資金研究成果実績報告書（慶應義塾大学) 2021
Variability of childhood and adolescent blood pressures using medical checkup data at Keio University and Keio affiliated schools

Azegami, Tatsuhiko

学事振興資金研究成果実績報告書（慶應義塾大学) 2020
The development of new therapeutic strategy for diabetic nephropathy

Azegami, Tatsuhiko

科学研究費補助金研究成果報告書 2020
Variability of childhood and adolescent blood pressures using medical checkup data at Keio University and Keio affiliated schools

Azegami, Tatsuhiko

学事振興資金研究成果実績報告書（慶應義塾大学) 2019
The development of new angiotensin II receptor vaccine

Azegami, Tatsuhiko

科学研究費補助金研究成果報告書 2015

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

慢性腎臓病に対する新規治療戦略の開発研究

2021.04

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2024.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator
糖尿病性腎症に対する新規治療戦略の開発

2018.04

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2021.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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Awards 【 Display / hide 】

第9回臨床高血圧フォーラム　Young Clinician Award 最優秀賞

2021.05

Type of Award： Award from Japanese society, conference, symposium, etc.
Asian-Pacific Society of Hypertension Young Investigator Fellowships

2018.10

Type of Award： Award from international society, conference, symposium, etc.
第8回臨床医学研究塾奨励賞

2017.10, 第8回臨床医学研究塾
Premium Hypertension Conference 優秀演題賞

2015.08, Premium Hypertension Conference
Asian-Pacific Society of Hypertension Young Investigator Fellowships

2012.10, International Society of Hypertension