1.High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction
Shun-ichiro ASAHARA ; Hiroyuki INOUE ; Yuka IHARA ; Kyoko TERUYAMA ; Asuka IMAI ; Chisako HARA ; Mizuki HARA ; Masako SEIKE ; Aisha YOKOI ; Nozomi KIDO ; Hirotaka SUZUKI ; Ayumi KANNO ; Yuka INABA ; Hitoshi WATANABE ; Go SHIOI ; Maki KIMURA-KOYANAGI ; Michihiro MATSUMOTO ; Hiroshi INOUE ; Keiichi I. NAKAYAMA ; Wataru OGAWA ; Masato KASUGA ; Yoshiaki KIDO
Diabetes & Metabolism Journal 2026;50(1):77-89
Background:
The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe.
Methods:
We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass.
Results:
In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass.
Conclusion
This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.
2.Screening of nontoxic dyes for improved visualization and success rate in mouse embryo transfer
Imai HIROYUKI ; Matsuya SUMITO ; Uemura TATSUMI ; Fujino KAORU ; Kawabe TOSHIAKI ; Kano KIYOSHI ; Kusakabe Ken TAKESHI
Laboratory Animal Research 2025;41(4):367-376
Background:
Advancements in genome editing technology and the globalization of life science research have highlighted the need for refined techniques in individualizing fertilized mouse eggs. Traditional embryo transfer surgery, which demands precise and objective success assessment, presents challenges for technical mastery and animal welfare. To address these issues, we developed a novel culture medium incorporating a dye library that enhances the visibility of ultrafine capillaries.
Results:
We screened 32 compounds based on their color properties and excluded those with clear cytotoxicity through colony formation inhibition tests. Five compounds demonstrated developmental outcomes comparable to those of the control group during embryo culture. Gene expression analysis revealed high correlation with control embryos, indicating no adverse developmental impact. No maternal toxicity was observed during and after embryo transfer using the dyed medium, which also produced normal offspring. A randomized survey confirmed improved visibility compared to conventional methods.
Conclusion
This study successfully identified nontoxic dyes that enhance the visibility of embryo transfer culture media, potentially improving precision and animal welfare in embryological research. Based on our findings, adding Brilliant Blue FCF or Fast Green FCF to the medium is recommended.
3.Clinical Outcomes of Biliary Drainage during a Neoadjuvant Therapy for Pancreatic Cancer: Metal versus Plastic Stents
Masaki KUWATANI ; Toru NAKAMURA ; Tsuyoshi HAYASHI ; Yasutoshi KIMURA ; Michihiro ONO ; Masayo MOTOYA ; Koji IMAI ; Keisuke YAMAKITA ; Takuma GOTO ; Kuniyuki TAKAHASHI ; Hiroyuki MAGUCHI ; Satoshi HIRANO ;
Gut and Liver 2020;14(2):269-273
Neoadjuvant chemotherapyeoadjuvant chemoradiotherapy (NAC/NACRT) can be performed in patients with pancreatic cancer to improve survival. We aimed to clarify the clinical outcomes of biliary drainage with a metal stent (MS) or a plastic stent (PS) during NAC/NACRT. Between October 2013 and April 2016, 96 patients with pancreatic cancer were registered for NAC/NACRT. Of these, 29 patients who underwent biliary drainage with MS or PS before NAC/NACRT and a subsequent pancreatoduodenectomy were retrospectively analyzed with regard to patient characteristics, preoperative recurrent biliary obstruction rate, NAC/NACRT delay or discontinuation rate, and operative characteristics. The median age of the patients was 67 years. NAC and NACRT were performed in 14 and 15 patients, respectively, and MS and PS were used in 17 and 12 patients, respectively. Recurrent biliary obstruction occurred in 6% and 83% of the patients in the MS and PS groups, respectively (p<0.001). NAC/NACRT delay was observed in 35% and 50% of the patients in the MS and PS groups, respectively (p=0.680). NAC/NACRT discontinuation was observed in 12% and 17% of the patients in the MS and PS groups, respectively (p=1.000). The operative time in the MS group tended to be longer than that in the PS group (625 minutes vs 497 minutes, p=0.051), and the operative blood loss volumes and postoperative adverse event rates were not different between the two groups. MS was better than PS from the viewpoint of preventing recurrent biliary obstruction, although MS was similar to PS with regards to perioperative outcomes.
4.Present Status of Endoscopic Submucosal Dissection for Non-Ampullary Duodenal Epithelial Tumors
Naomi KAKUSHIMA ; Masao YOSHIDA ; Yohei YABUUCHI ; Noboru KAWATA ; Kohei TAKIZAWA ; Yoshihiro KISHIDA ; Sayo ITO ; Kenichiro IMAI ; Kinichi HOTTA ; Hirotoshi ISHIWATARI ; Hiroyuki MATSUBAYASHI ; Hiroyuki ONO
Clinical Endoscopy 2020;53(6):652-658
Prediction of histology by endoscopic examination is important in the clinical management of non-ampullary duodenal epithelial tumors (NADETs), including adenoma and adenocarcinoma. The use of a simple scoring system based on the findings of white-light endoscopy or magnified endoscopy with narrow-band imaging is useful to differentiate between Vienna category 3 (C3) and C4/5 lesions. Less invasive endoscopic resection procedures, such as cold snare polypectomy, are quick to perform and convenient for small (<10 mm) C3 lesions. Neoplasms with higher grade histology, such as C4/5 lesions, should be treated by endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or surgery. Although EMR often requires piecemeal resection, the complication rate is acceptable. Excellent complete resection rates could be achieved by ESD; however, it remains a challenging method considering the high risk of complications. Shielding or closure of the ulcer after ESD is effective at decreasing the risk of delayed bleeding and perforation. Laparoscopic endoscopic cooperative surgery is an ideal treatment with a high rate of en bloc resection and a low rate of complications, although it is limited to high-volume centers. Patients with NADETs could benefit from a multidisciplinary approach to stratify the optimal treatment based on endoscopic diagnoses.
5.Comparison of the Diagnostic Yield of the Standard 22-Gauge Needle and the New 20-Gauge Forward-Bevel Core Biopsy Needle for Endoscopic Ultrasound-Guided Tissue Acquisition from Pancreatic Lesions
Shinya FUJIE ; Hirotoshi ISHIWATARI ; Keiko SASAKI ; Junya SATO ; Hiroyuki MATSUBAYASHI ; Masao YOSHIDA ; Sayo ITO ; Noboru KAWATA ; Kenichiro IMAI ; Naomi KAKUSHIMA ; Kohei TAKIZAWA ; Kinichi HOTTA ; Hiroyuki ONO
Gut and Liver 2019;13(3):349-355
BACKGROUND/AIMS: To compare the diagnostic yield of 20-gauge forward-bevel core biopsy needle (CBN) and 22-gauge needle for endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) of solid pancreatic masses. METHODS: The use of 20-gauge CBN was prospectively evaluated for 50 patients who underwent EUS-FNA from June 2016 to December 2016. Data were compared with those obtained by a retrospective study of 50 consecutive patients who underwent EUS-FNA using standard 22-gauge needles between December 2016 and April 2017. At least two punctures were performed for each patient; the sample from the first pass was used for cytology with or without histology and that from the second pass was used for histology. Sample quantity was evaluated using the sample obtained from the second pass. RESULTS: There was no significant difference in the diagnostic accuracy rate between the first and second passes (20-gauge CBN: 96% [48/50]; standard 22-gauge needle: 88% [44/50]). Samples >10× power fields in length were obtained from 90% (43/48) and 60% (30/50) of patients using the 20-gauge CBN and standard 22-gauge needle, respectively (p=0.01). Technical failure occurred for two patients with the 20-gauge CBN. CONCLUSIONS: Diagnostic accuracy of the 20-gauge CBN was comparable to that of the 22-gauge needle. However, two passes with the 20-gauge CBN yielded a correct diagnosis for 100% of patients when technically feasible. Moreover, the 20-gauge CBN yielded core tissue for 90% patients, which was a performance superior to that of the 22-gauge needle.
Biopsy
;
Biopsy, Fine-Needle
;
Diagnosis
;
Endoscopic Ultrasound-Guided Fine Needle Aspiration
;
Humans
;
Needles
;
Pancreas
;
Prospective Studies
;
Punctures
;
Retrospective Studies
;
Ultrasonography
6.A Case of Axillofemoral Bypass Graft Stump Syndrome Occurring in Both the Upper and Lower Extremities
Shinya NEGOTO ; Ryo KANAMOTO ; Shinichi NATA ; Shinichi IMAI ; Yusuke SHINTANI ; Hiroyuki OTSUKA ; Shinichi HIROMATSU ; Hidetoshi AKASHI ; Hiroyuki TANAKA
Japanese Journal of Cardiovascular Surgery 2019;48(4):277-280
Acute ischemia due to thromboembolism caused by occluded prosthetic graft after axillary-femoral artery bypass has been reported as axillofemoral bypass graft stump syndrome (AxSS). AxSS usually occurs in the upper extremities and it is rare that it occurs in the lower extremities. We encountered a rare case of a 76-year-old woman with acute right upper and lower extremities ischemia 4 years after right axillary-external iliac artery bypass grafting. The graft and the native arteries of the right upper and lower limbs were occluded. In addition, the right axillary artery and proximal anastomotic site were deformed. We diagnosed acute limb ischemia due to AxSS and immediately performed thrombectomy. Because we considered the thrombosis to originate from the axillary-iliac artery bypass graft, we disconnected the occluded graft from the native arteries. Six months after surgery, she was doing well without recurrence of thromboembolism. We report here the successful treatment of a case of AxSS that developed in both the upper and lower extremities.
7.Popliteal Artery Adventitia Cyst
Shohei Yoshida ; Shinichi Hiromatsu ; Kentaro Sawada ; Takahiro Shojima ; Ryo Kanamoto ; Shinichi Imai ; Hiroyuki Otsuka ; Hiroyuki Tanaka
Japanese Journal of Cardiovascular Surgery 2017;46(4):182-185
A 60 year old man presented with a history of right leg claudication which occurred after walking a distance of 200 m. He had no history of cardiovascular risk factors or trauma in the lower extremities. Palpation disclosed no right popliteal or pedal pulse. Ankle-brachial pressure index (ABI) was 0.60 on the affected side. Computed tomography (CT) demonstrated the presence of a highly stenotic lesion in the right popliteal artery due to compression from periarterial polycystic masses. Magnetic resonance imaging (MRI) revealed no communication to the knee joint bursa. Further, angiography showed a beak-like severe stenosis on the knee of the right popliteal artery. Based on the results of these three imaging techniques we confirmed the diagnosis of cystic adventitial disease (CAD). The patient underwent a surgical exploration of his popliteal artery through a posterior approach. Evacuation of all cysts by longitudinal incision of his adventitia yielded yellow mucoid gelatinous material. The popliteal artery was replaced using the great saphenous vein because the previous imaging showed thrombus formation at the cyst site. He had an uneventful postoperative recovery with ABI of 1.10.
8.A Surgical Case of Residual Axillary Artery Aneurysm Associated with Kawasaki Disease
Kentaro Sawada ; Yukio Hosokawa ; Hinako Sakurai ; Ryo Kanamoto ; Shinichi Imai ; Yusuke Shintani ; Shinichi Nata ; Shinichi Hiromatsu ; Hidetoshi Akashi ; Hiroyuki Tanaka
Japanese Journal of Cardiovascular Surgery 2017;46(6):320-324
We herein report on a case in which we conducted bypass surgery for occlusion of a left axillary artery aneurysm with ischemic symptoms 21 years after the contraction of Kawasaki disease and achieved symptomatic improvement. The case involved a 22-year-old man who had been suffering from Kawasaki disease since the age of one. He had been undergoing antiplatelet therapy for bilateral axillary artery aneurysms by orally taking aspirin for 20 years. He suffered from symptoms of upper limb ischemia 21 years after receiving a diagnosis of peripheral aneurysms and occlusion of a left axillary artery aneurysm upon 3DCTA. We conducted aneurysmotomy, plication, and bypass surgery between the axillary and brachial arteries via the autologous vein. Pathological examination revealed due to the formation of atheroma in the tunica intima and disarrangement of the layer structure in the tunica media : thickening of the tunica media was partially observed. His fatigue upon exertion of his left upper extremity remarkably improved following surgery. Although peripheral aneurysms associated with Kawasaki disease are rare, as seen in this case, peripheral arterial disease remains and progresses even after long periods of time. It is believed necessary to carry out long term follow-up and examine the approaches to therapy including surgery in accordance with the site and degree of the disease.
9.Natural History of Early Gastric Cancer: a Case Report and Literature Review.
Tomohiro IWAI ; Masao YOSHIDA ; Hiroyuki ONO ; Naomi KAKUSHIMA ; Kohei TAKIZAWA ; Masaki TANAKA ; Noboru KAWATA ; Sayo ITO ; Kenichiro IMAI ; Kinichi HOTTA ; Hirotoshi ISHIWATARI ; Hiroyuki MATSUBAYASHI
Journal of Gastric Cancer 2017;17(1):88-92
Early detection and treatment decrease the mortality rate associated with gastric cancer (GC). However, the natural history of GC remains unclear. An 85-year-old woman was referred to our hospital for evaluation of a gastric tumor. Esophagogastroduodenoscopy identified a 6 mm, flat-elevated lesion at the lesser curvature of the antrum. A biopsy specimen showed a well-differentiated tubular adenocarcinoma. The depth of the lesion was estimated to be intramucosal. Although the lesion met the indications for endoscopic resection, periodic endoscopic follow-up was performed due to the patient's advanced age and comorbidities. The mucosal GC invaded into the submucosa 3 years later, and finally progressed to advanced cancer 5 years after the initial examination. The patient died of tumor hemorrhage 6.4 years after the initial examination. In this case, mucosal GC progressed to advanced GC, eventually leading to the patient's death from GC. Early and appropriate treatment is required to prevent GC-related death.
Adenocarcinoma
;
Aged, 80 and over
;
Biopsy
;
Comorbidity
;
Endoscopy, Digestive System
;
Female
;
Follow-Up Studies
;
Hemorrhage
;
Humans
;
Mortality
;
Natural History*
;
Stomach Neoplasms*
10.Infected Abdominal Aortic Aneurysm with a Previous History of Coronary Artery Bypass Grafting with the Right Gastroepiploic Artery
Shinichi Imai ; Kentaro Sawada ; Eiji Nakamura ; Shohei Yoshida ; Hayato Fukuda ; Satoru Tobinaga ; Seiji Onitsuka ; Shinichi Hiromatsu ; Hidetoshi Akashi ; Hiroyuki Tanaka
Japanese Journal of Cardiovascular Surgery 2016;45(2):84-88
We report a case of successful anatomical reconstruction with omentopexy of an infected abdominal aortic aneurysm (AAA) in a patient with a previous history of coronary artery bypass grafting with the right gastroepiploic artery. A 60-year-old man was referred to our institute because of fever and abdominal pain during hemodialysis for chronic renal failure. Antibiotic therapy was started after computed tomography revealed an infected abdominal aortic aneurysm. After infection control, surgical treatment was scheduled. At surgery, left axillo-bifemoral bypass was performed first, because it was unclear whether the omentum was large enough for omentopexy. At laparotomy, adequate omentum and infective AAA were confirmed. AAA repair using a rifampicin-soaked graft, and omentopexy were performed. Enterobacter aerogenes was detected from the resected aortic wall. After the operation, intravenous antibiotic was used for 25 days until CRP was normalized. One year follow-up showed no sign of re-infection.


Result Analysis
Print
Save
E-mail