المؤلفون: Eiji Kawasaki, Takuya Awata, Hiroshi Ikegami, Akihisa Imagawa, Yoichi Oikawa, Haruhiko Osawa, Takeshi Katsuki, Norio Kanatsuna, Ryoichi Kawamura, Junji Kozawa, Noriko Kodani, Tetsuro Kobayashi, Akira Shimada, Masayuki Shimoda, Kazuma Takahashi, Daisuke Chujo, Tetsuro Tsujimoto, Kyoichiro Tsuchiya, Aiko Terakawa, Jungo Terasaki, Kan Nagasawa, Shinsuke Noso, Tomoyasu Fukui, Ichiro Horie, Kazuki Yasuda, Hisafumi Yasuda, Hidekatsu Yanai, Toshiaki Hanafusa, Hiroshi Kajio, the Japanese Type 1 Diabetes Database Study (TIDE‐J)

المصدر: Journal of Diabetes Investigation, Vol 15, Iss 7, Pp 835-842 (2024)

مصطلحات موضوعية: Glutamic acid decarboxylase, Prediction, Slowly‐progressive type 1 diabetes, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Abstract Aims/Introduction This study aimed to identify risk factors that contribute to the progression of slowly‐progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin‐dependent state. Materials and Methods We selected 60 slowly‐progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) techniques. Results Compared with the non‐progressor group (fasting C‐peptide [F‐CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F‐CPR levels and a higher prevalence of insulinoma‐associated antigen‐2 autoantibodies (IA‐2A). The PPV of RIA‐GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2040-1116Test; https://doaj.org/toc/2040-1124Test

الوصول الحر: https://doaj.org/article/2548a80a84c24af5abc976218388891eTest

المؤلفون: Keiichiro Matoba, Yosuke Nagai, Kensuke Sekiguchi, Shinji Ohashi, Etsuko Mitsuyoshi, Masayuki Shimoda, Toshiaki Tachibana, Daiji Kawanami, Tamotsu Yokota, Kazunori Utsunomiya, Rimei Nishimura

المصدر: Communications Biology, Vol 7, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Abstract Focal segmental glomerulosclerosis (FSGS) shares podocyte damage as an essential pathological finding. Several mechanisms underlying podocyte injury have been proposed, but many important questions remain. Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) is a serine/threonine kinase responsible for a wide array of cellular functions. We found that ROCK2 is activated in podocytes of adriamycin (ADR)-induced FSGS mice and cultured podocytes stimulated with ADR. Conditional knockout mice in which the ROCK2 gene was selectively disrupted in podocytes (PR2KO) were resistant to albuminuria, glomerular sclerosis, and podocyte damage induced by ADR injection. In addition, pharmacological intervention for ROCK2 significantly ameliorated podocyte loss and kidney sclerosis in a murine model of FSGS by abrogating profibrotic factors. RNA sequencing of podocytes treated with a ROCK2 inhibitor proved that ROCK2 is a cyclic nucleotide signaling pathway regulator. Our study highlights the potential utility of ROCK2 inhibition as a therapeutic option for FSGS.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2399-3642Test

الوصول الحر: https://doaj.org/article/2bd38aa5657c4c588e38e29badb7fe47Test

المؤلفون: Chika Yamada, MD, Akira Baba, MD, PhD, Hideomi Yamauchi, MD, PhD, Nobuhiro Ogino, MD, PhD, Masato Nagaoka, MD, Ai Iwauchi, MD, Miku Maeda, MD, Nei Fukasawa, MD, Masayuki Shimoda, MD, PhD, Taisuke Mori, MD, PhD, Hiroya Ojiri, MD, PhD

المصدر: Radiology Case Reports, Vol 18, Iss 11, Pp 4160-4166 (2023)

مصطلحات موضوعية: Carcinoma ex pleomorphic adenoma, Epithelial-myoepithelial, Parotid gland, Case report, Radiologic-pathologic, Medical physics. Medical radiology. Nuclear medicine, R895-920

الوصف: Carcinoma ex pleomorphic adenoma is a carcinoma that arises from a primary or recurrent benign pleomorphic adenoma. The prevalence of epithelial-myoepithelial carcinoma is low, and this histological type accounting for only 1% of all salivary gland tumors. Here, we report a rare case of Epithelial-Myoepithelial Carcinoma ex pleomorphic adenoma of the parotid gland with a radiologic-pathologic correlation.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1930043323006192Test; https://doaj.org/toc/1930-0433Test

الوصول الحر: https://doaj.org/article/d1ab30c263604b5aaea9cc57ab185815Test

المؤلفون: Kentaro Kasa, MD, Takao Ohki, MD, PhD, Eisaku Ito, MD, PhD, Nei Fukasawa, MD, Kota Shukuzawa, MD, PhD, Masayuki Shimoda, MD, PhD

المصدر: Journal of Vascular Surgery Cases and Innovative Techniques, Vol 10, Iss 1, Pp 101377- (2024)

مصطلحات موضوعية: Hepatic artery aneurysm, Immunoglobulin G4-related disease, Visceral artery aneurysm, Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: A 49-year-old man who was a current smoker with a history of hypertension, dyslipidemia, and coronary artery disease after coronary stent placement presented because of abdominal and back pain. Contrast-enhanced computed tomography showed a 30-mm, large hepatic artery aneurysm. Resection of the aneurysm and autogenous vein bypass grafting was performed, which resulted in a successful outcome without any complications. Pathologic examination of the aneurysm confirmed that it was related to immunoglobulin G4 (IgG4). The patient's serum IgG4 level was within the normal range, and no other signs of IgG4-related organ lesions were observed.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2468428723002861Test; https://doaj.org/toc/2468-4287Test

الوصول الحر: https://doaj.org/article/d0b6a083bb644d0aba278c814f4953f5Test

المؤلفون: Noriko Kodani, Daisuke Chujo, Aiko Terakawa, Kyoji Ito, Fuyuki Inagaki, Nobuyuki Takemura, Shinichi Matsumoto, Tsuyoshi Tajima, Norio Ohmagari, Kumiko Ajima, Tadashi Takaki, Yzumi Yamashita, Koya Shinohara, Hiroshi Kajio, Takuya Awata, Masayuki Shimoda

المصدر: Journal of Diabetes Investigation, Vol 14, Iss 5, Pp 725-729 (2023)

مصطلحات موضوعية: Autoimmunity, Islet transplantation, Type 1 diabetes mellitus, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: ABSTRACT Pancreatic islet transplantation is a β‐cell replacement therapy for people with insulin‐deficient diabetes who have difficulty in glycemic control and suffer from frequent severe hypoglycemia. However, the number of islet transplantations carried out is still limited in Asia. We report a case of allogeneic islet transplantation in a 45‐year‐old Japanese man with type 1 diabetes. Although the islet transplantation was successfully carried out, graft loss was observed on the 18th day. Immunosuppressants were used in accordance with the protocol, and donor‐specific anti‐human leukocyte antigen antibodies were not detected. Autoimmunity relapse was also not observed. However, the patient had a high titer of anti‐glutamic acid decarboxylase antibody from before the islet transplantation, and autoimmunity might thus have affected the β‐cells in the transplanted islet. The evidence is still scarce to reach conclusions, and further data accumulation is required to enable proper patient selection before islet transplantation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2040-1116Test; https://doaj.org/toc/2040-1124Test

الوصول الحر: https://doaj.org/article/48291c2bb3494a77b971f1f975528002Test

المؤلفون: Kaoru Takabayashi, Masayuki Shimoda, Takanori Kanai, Yasushi Iwao

المصدر: Internal Medicine. 2023, 62(20):3085

المؤلفون: Shun Sato, Takahiro Kimura, Hajime Onuma, Shin Egawa, Masayuki Shimoda, Hiroyuki Takahashi

المصدر: BJUI Compass, Vol 4, Iss 2, Pp 234-240 (2023)

مصطلحات موضوعية: cribriform pattern, Gleason score, pathological marker, percentage of Gleason Pattern 4, prognostic factor, prostate cancer, Diseases of the genitourinary system. Urology, RC870-923

الوصف: Abstract Objectives This study aims to clarify the clinicopathological significance of several novel pathological markers, including the percentage of Gleason pattern 4 and small/non‐small cribriform pattern, in intermediate‐risk Gleason score 3 + 4 = 7 prostate cancer. Subjects and Methods Two‐hundred and twenty‐eight patients with Gleason score 3 + 4 = 7 intermediate‐risk prostate cancer who underwent radical prostatectomy between 2009 and 2019 at our institute were selected. Preoperative clinicopathological characteristics, including serum prostate‐specific antigen level, clinical T stage, percentage of cancer‐positive cores at biopsy, small/non‐small cribriform pattern, the highest percentage of Gleason pattern 4, the total length of Gleason pattern 4 and percentage of Gleason score 7 cores were examined in univariate/multivariate logistic regression analysis to determine their predictive value for postoperative adverse pathological findings, defined as an upgrade to Gleason score 4 + 3 = 7 or higher, pN1 or pT3b disease. Results Fifty‐four cases (23.7%) showed adverse pathological findings. Although a non‐small cribriform pattern, highest Gleason pattern 4 percentage and total length of Gleason pattern 4 were predictive of adverse pathological findings in univariate analysis, only the highest Gleason pattern 4 percentage was an independent predictive factor in multivariate analysis (odds ratio: 1.610; 95% confidence interval: 1.260–2.070; P = 0.0002). Conclusion The highest Gleason pattern 4 percentage was a potent predictive parameter for Gleason score 3 + 4 = 7 intermediate‐risk prostate cancer and should be considered in the risk classification scheme for prostate cancer.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2688-4526Test

الوصول الحر: https://doaj.org/article/70b691209b7346ed98f094f4df880d7eTest

المؤلفون: Yoshiro Tanaka, Tomohisa Nagoshi, Hirotake Takahashi, Yuhei Oi, Rei Yasutake, Akira Yoshii, Haruka Kimura, Yusuke Kashiwagi, Toshikazu D. Tanaka, Masayuki Shimoda, Michihiro Yoshimura

المصدر: iScience, Vol 26, Iss 9, Pp 107730- (2023)

مصطلحات موضوعية: Cell biology, Pathophysiology, Physiology, Science

الوصف: Summary: We recently reported that the selective inhibition of urate transporter-1 (URAT1), which is primarily expressed in the kidneys, ameliorates insulin resistance by attenuating hepatic steatosis and improving brown adipose tissue function in diet-induced obesity. In this study, we evaluated the effects of dotinurad, a URAT1-selective inhibitor, on the hearts of high-fat diet (HFD)-fed obese mice for 16–20 weeks and on neonatal rat cardiomyocytes (NRCMs) exposed to palmitic acid. Outside the kidneys, URAT1 was also expressed in cardiomyocytes and indeed worked as a uric acid transporter. Dotinurad substantially attenuated HFD-induced cardiac fibrosis, inflammatory responses, and cardiac dysfunction. Intriguingly, among various factors related to the pathophysiology of diet-induced obesity, palmitic acid significantly increased URAT1 expression in NRCMs and subsequently induced apoptosis, oxidative stress, and inflammatory responses via MAPK pathway, all of which were reduced by dotinurad. These results indicate that URAT1 is a potential therapeutic target for metabolic heart disease.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589004223018072Test; https://doaj.org/toc/2589-0042Test

الوصول الحر: https://doaj.org/article/d3ca071ededb4a32b53ae9e2375ad775Test

المؤلفون: Hiroshi Kamioka, Satomi Yogosawa, Tsunekazu Oikawa, Daisuke Aizawa, Kaoru Ueda, Chisato Saeki, Koichiro Haruki, Masayuki Shimoda, Toru Ikegami, Yuji Nishikawa, Masayuki Saruta, Kiyotsugu Yoshida

المصدر: JHEP Reports, Vol 5, Iss 7, Pp 100759- (2023)

مصطلحات موضوعية: DYRK2, HCC, Liver cancer, Animal model, Carcinogenesis, HTVi, Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: Background & Aims: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and has a poor prognosis. However, the molecular mechanisms underlying hepatocarcinogenesis and progression remain unknown. In vitro gain- and loss-of-function analyses in cell lines and xenografts revealed that dual-specificity tyrosine-regulated kinase 2 (DYRK2) influences tumour growth in HCC. Methods: To investigate the role of Dyrk2 during hepatocarcinogenesis, we developed liver-specific Dyrk2 conditional knockout mice and an in vivo gene delivery system with a hydrodynamic tail vein injection and the Sleeping Beauty transposon. The antitumour effects of Dyrk2 gene transfer were investigated in a murine autologous carcinogenesis model. Results: Dyrk2 expression was reduced in tumours, and that its downregulation was induced before hepatocarcinogenesis. Dyrk2 gene transfer significantly suppressed carcinogenesis. It also suppresses Myc-induced de-differentiation and metabolic reprogramming, which favours proliferative, and malignant potential by altering gene profiles. Dyrk2 overexpression caused Myc and Hras degradation at the protein level rather than at the mRNA level, and this degradation mechanism was regulated by the proteasome. Immunohistochemical analyses revealed a negative correlation between DYRK2 expression and MYC and longer survival in patients with HCC with high-DYRK2 and low-MYC expressions. Conclusions: Dyrk2 protects the liver from carcinogenesis by promoting Myc and Hras degradation. Our findings would pave the way for a novel therapeutic approach using DYRK2 gene transfer. Impact and Implications: Hepatocellular carcinoma (HCC) is one of the most common cancers, with a poor prognosis. Hence, identifying molecules that can become promising targets for therapies is essential to improve mortality. No studies have clarified the association between DYRK2 and carcinogenesis, although DYRK2 is involved in tumour growth in various cancer cells. This is the first study to show that Dyrk2 expression decreases during hepatocarcinogenesis and that Dyrk2 gene transfer is an attractive approach with tumour suppressive activity against HCC by suppressing Myc-mediated de-differentiation and metabolic reprogramming that favours proliferative and malignant potential via Myc and Hras degradation.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589555923000903Test; https://doaj.org/toc/2589-5559Test

الوصول الحر: https://doaj.org/article/8a96d16c8f1e46e4a5c3c9e21b89f400Test

المؤلفون: Daisuke Chujo, Toshiaki Kurokawa, Akitsu Kawabe, Nobuyuki Takahashi, Fuyuki Inagaki, Koya Shinohara, Shotaro Hagiwara, Yoshihiro Edamoto, Norio Ohmagari, Fumihiko Hinoshita, Tsuyoshi Tajima, Hiroshi Kajio, Hiroshi Ohtsu, Nobuyuki Takemura, Shinichi Matsumoto, Masayuki Shimoda

المصدر: Journal of Diabetes Investigation, Vol 13, Iss 4, Pp 741-745 (2022)

مصطلحات موضوعية: Autoimmune response, Type 1 diabetes mellitus, Islet transplantation, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Abstract Here, we report a case of allogeneic islet transplantation in Japan. A 48‐year‐old man received intraportal islet transplantation (5,945 islet equivalent/kg), and stabilization of blood glucose levels and suppression of hypoglycemia were achieved. In the present case, we used our original assessment method to detect the responses of the recipient’s T cells to islet autoantigens over time to monitor cellular autoimmunity. Other markers could not predict graft dysfunction in advance, but our method detected the activation of islet antigen‐specific CD8+ T‐cell responses before the deterioration of pancreatic β‐cell function, indicating the possibility of the non‐invasive detection of pancreatic β‐cell damage due to recurrent autoimmunity.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2040-1116Test; https://doaj.org/toc/2040-1124Test

الوصول الحر: https://doaj.org/article/24301e867dee4c72a63e191cf0743177Test