Publications by authors named "Kouhei Tsuchida"
Article Synopsis
- High-level activation of NRF2, often due to mutations in the NRF2 gene, is common in esophageal squamous cell carcinoma (ESCC), while mutations in KEAP1, which normally suppresses NRF2, do not lead to similar outcomes.
- Researchers aim to create a mouse model that mimics NRF2-activated ESCC by combining NRF2 mutations with TRP53 mutations, resulting in lesions similar to ESCC.
- The study indicates that while both KEAP1-deleted cells and cells with activated NRF2 show increased NRF2 levels, their outcomes differ significantly, with KEAP1 loss leading to cell disappearance rather than lesion formation, highlighting the importance of NRF2 in ESCC development.
Nrf2 activates cytoprotective gene expression, and Nrf2 activity is regulated through at least two protein degradation pathways: the Keap1-mediated and β-TrCP-mediated pathways. To address the relative contributions of these pathways, we generated knock-in mouse lines expressing an Nrf2 mutant that harbored two substitution mutations of serine residues interacting with β-TrCP. The homozygous () mice grew normally, with Nrf2 levels comparable to those of wild-type (WT) mice under unstressed conditions.
View Article and Find Full Text PDFNrf2 is essential for cytoprotection against carcinogens, and through systemic Nrf2 knockout mice, Nrf2-deficient cells were shown to be susceptible to chemical carcinogens and prone to developing cancers. However, the oncogenic potential of Nrf2-deficient epithelial cells surrounded by normal cells in the esophagus could not be assessed by previous models, and the fate of Nrf2-deficient cells in such situations remains elusive. In this study, therefore, we generated mice that harbor almost equal levels of cells with Nrf2 deleted and those with Nrf2 intact in the basal layer of the esophageal epithelium, utilizing inducible Cre-mediated recombination of alleles in adults through moderate use of tamoxifen.
View Article and Find Full Text PDFA Case of Bilateral Acute Inferior Limb Ischemia in a Patient With Ulcerative Colitis.
Clin Med Insights Case Rep
March 2020
Article Synopsis
- - A patient with ulcerative colitis (UC) experienced a relapse in 2015, which included symptoms like abdominal pain, diarrhea, and bloody stools.
- - She later developed acute ischemia in both lower limbs, confirmed by imaging, and underwent a surgical procedure to restore blood flow.
- - The case highlights the link between UC and increased risk of thrombosis, emphasizing the need for careful monitoring and preventive treatment for both bleeding and clotting risks in severe UC cases.
Article Synopsis
- Extension of inflammation from acute pancreatitis to the scrotum is uncommon but can be serious.* -
- If it does occur, the resulting inflammation in the scrotum can become severe.* -
- Doctors should consider this as a potential complication and may need to conduct imaging tests for patients experiencing cyst swelling or testicular pain.*
Article Synopsis
- * A study of 89 UC patients evaluated the effects of white blood cell count (WBC) and mean cell volume (MCV) as indicators for withdrawing IMs, finding better remission rates in those who continued IM treatment versus those who stopped.
- * Achieving mucosal healing (MH) was linked to higher remission maintenance rates, suggesting that monitoring for MH could help determine the timing of IM withdrawal effectively.
Objective: There is no consensus regarding administration of propofol for performing endoscopic submucosal dissection (ESD) in patients with comorbidities. The aim of this study was to evaluate the safety and efficacy of propofol-induced sedation administered by nonanesthesiologists during ESD of gastric cancer in patients with comorbidities classified according to the American Society of Anesthesiologists (ASA) physical status.
Methods: Five hundred and twenty-two patients who underwent ESD for gastric epithelial tumors under sedation by nonanesthesiologist-administrated propofol between April 2011 and October 2017 at Dokkyo Medical University Hospital were enrolled in this study.
Article Synopsis
- There is no agreed-upon best method for obtaining deep tissue biopsies for advanced gastric linitis plastica (LP), but endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) shows promise as a diagnostic tool.
- A 46-year-old male with suspected advanced gastric LP had inconclusive results from initial biopsies, but EUS-FNA ultimately revealed signet ring cell carcinoma, leading to a chemotherapy referral.
- The case highlights that EUS-FNA is a potentially effective and less invasive option for diagnosing advanced gastric LP, suggesting it should be considered for deep tissue biopsy collection.
Background And Study Aims: Endoscopic submucosal dissection (ESD) is a technically advanced procedure for colorectal tumors. Hayashi et al. invented the "pocket-creation method (PCM)," and reported that Is-type lesions with fibrosis could be efficaciously and safely resected.
View Article and Find Full Text PDFArticle Synopsis
- * In May 2015, upper endoscopy revealed two elevated lesions in the gastric fundus that were later removed via ESD.
- * The lesions were diagnosed as gastric adenocarcinoma of the fundic gland type, which emerged after previous treatments and appeared in a previously atrophied area that had improved post-therapy.
Article Synopsis
- This study compares endoscopic nasobiliary drainage (ENBD) and endoscopic biliary stent (EBS) as preoperative treatments for hilar malignant biliary obstruction (MBO) using data from 374 cases across 29 centers.
- The research found that while ENBD had a high technical success rate (94.6%), 21.9% of patients experienced adverse events, and over half (61.5%) required preoperative re-interventions, mostly unplanned.
- Ultimately, the analysis suggests that ENBD does not offer significant advantages over EBS, and unplanned re-interventions are linked to poorer outcomes for patients with resectable hilar MBO.
Article Synopsis
- A 53-year-old man was diagnosed with a neuroendocrine tumor of unknown origin and multiple liver metastases after experiencing diarrhea and low potassium levels.
- Treatment with somatostatin analogues initially reduced tumor size and improved symptoms, but the tumors eventually regrew and symptoms recurred.
- Following a procedure called transcatheter arterial embolization (TAE), the patient's symptoms disappeared, and although the tumor was not removable, he achieved long-term survival with the help of chemotherapy and TAE.
The KEAP1-NRF2 system regulates the cellular defence against oxidative and xenobiotic stresses. NRF2 is a transcription factor that activates the expression of cytoprotective genes encoding antioxidative, detoxifying and metabolic enzymes as well as transporters. Under normal conditions, KEAP1 represses NRF2 activity by degrading the NRF2 protein.
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- The study explores a copper-catalyzed method for enantioselectively propargylating indoles using propargylic esters.
- This process is followed by a sequential Huisgen cycloaddition with azides, resulting in the formation of chiral triarylmethanes featuring a quaternary carbon center.
- The findings suggest potential applications for creating tetraarylmethanes with high to excellent enantioselectivity.
Article Synopsis
- The Nrf2-small Maf (sMaf) heterodimer is crucial for activating protective genes when cells face oxidative and toxic stress by binding to specific DNA elements known as CsMBE (CNC-sMaf binding element).
- Researchers modified a key position in the Nrf2 protein, resulting in a version that binds to different DNA sequences (MARE) and altered its target sites, demonstrating a shift from its typical binding behavior.
- The modified Nrf2 variant showed reduced ability to activate essential protective genes, making mutant mice more susceptible to liver damage from acetaminophen, underscoring the unique importance of CsMBE for Nrf2-sMaf function in cellular defense.
Amelioration of inflammation and tissue damage in sickle cell model mice by Nrf2 activation.
Proc Natl Acad Sci U S A
September 2015
Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β-globin gene, leading to the production of abnormally shaped red blood cells. Sickle cells are prone to hemolysis and thereby release free heme into plasma, causing oxidative stress and inflammation that in turn result in damage to multiple organs. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is a master regulator of the antioxidant cell-defense system.
View Article and Find Full Text PDFBackground: Endoscopic sphincterotomy (EST) is currently recognized as the primary endoscopic treatment for common bile duct stones. However, it is difficult to remove multiple (≥ 3) or large (≥ 15 mm) common bile duct stones with EST alone. Recently, EST plus endoscopic papillary large-balloon dilation (EPLBD) was reported to be an effective treatment for such bile duct stones.
View Article and Find Full Text PDFArticle Synopsis
- GATA1 is a crucial transcription factor for the development of red blood cells and platelets, and its knockdown in certain mice leads to leukemia.
- Researchers created a new cell line called GAK14 from leukemia cells in these mice, which can produce some hematopoietic cells but not erythroid or megakaryocytic lineages without additional components.
- The study highlights that GAK14 cells can differentiate into mature red blood cells when given full GATA1, but not when the GATA1 N-terminal domain is missing, underscoring its importance in this differentiation process.