Publications by authors named "Koji Saito"
Iqsec1 (IQ motif and Sec7 domain-containing protein 1), also known as BRAG2 (Brefeldin A-resistant Arf-GEF 2), is a guanine nucleotide exchange factor that regulates membrane trafficking, cytoskeletal organization, and signal transduction by activating class II and III ADP-ribosylation factors. To investigate the physiological role of Iqsec1 at the whole animal level, we generated Iqsec1-deficient mice using CRISPR/Cas9-mediated gene editing. Nearly all Iqsec1 mice (99%) exhibited embryonic lethality with severe growth retardation.
View Article and Find Full Text PDFNovel germline STAT3 gain-of-function mutation causes autoimmune diseases and severe growth failure.
J Allergy Clin Immunol Glob
November 2024
Article Synopsis
- The study investigates a young boy with severe autoimmune conditions who was found to have a germline gain-of-function mutation in the STAT3 gene through whole-exome sequencing.* -
- Treatment with the targeted therapy tocilizumab led to a reduction in hospital stays and slowed the progression of pulmonary fibrosis, showing promise for managing his condition without increasing steroid use.* -
- The findings suggest that genetic testing and functional analysis of STAT3 mutations are important for diagnosing early-onset autoimmune diseases and for considering targeted treatment options.*
Background: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability.
View Article and Find Full Text PDFEarly detection of necrosis in low-enhanced pancreatic parenchyma using contrast-enhanced computed tomography was a better predictor of clinical outcomes than pancreatic inflammation: A multicentric cohort study of severe acute pancreatitis.
Tomonori Yamamoto Masayasu Horibe Masamitsu Sanui Mitsuhito Sasaki Yasumitsu Mizobata Koji Saito Shinjiro Saito
Pancreatology
September 2024
Article Synopsis
- The study aimed to evaluate how well contrast-enhanced computed tomography (CECT) predicts outcomes for patients with severe acute pancreatitis (SAP) by using the computed tomography severity index (CTSI).
- A retrospective analysis of 1,097 SAP patients from 44 institutions in Japan found that while necrosis in pancreatic tissue increased mortality risks, the overall inflammation did not significantly impact mortality rates.
- The results showed that the CTSI had a moderate ability (AUC 0.65) to predict mortality, with significant correlations between higher levels of pancreatic necrosis and increased odds of death.
Article Synopsis
- Lipopolysaccharide (LPS) from Gram-negative bacteria activates Toll-like receptors (TLRs) and may affect locomotion in mice when exposed to new environments, with Porphyromonas gingivalis (Pg) LPS's influence being previously unknown.
- In this study, researchers compared the effects of Pg-LPS and Escherichia coli (Ec-LPS) on mouse locomotion and blood levels of inflammatory markers IL-6, TNF-alpha, and IL-10, using a TLR4 antagonist (TAK-242) to assess TLR4's role.
- Results showed that while Ec-LPS inhibited locomotion and increased IL-6 and IL-10 levels, Pg-LPS did not produce
Article Synopsis
- The study focuses on kidney podocytes and how their function relies on the actin cytoskeleton regulated by Rho small GTPases, highlighting that podocyte dysfunction is linked to kidney diseases and proteinuria.
- FilGAP, a protein that activates Rho small GTPase Rac1, is essential for maintaining podocyte structure, as its depletion leads to a loss of actin stress fibers and reduced cell adhesion.
- The research demonstrates that FilGAP helps podocytes form necessary structures and attachments to the extracellular matrix by inhibiting Rac1 and PAK1 signaling pathways, suggesting its critical role in preventing kidney-related pathologies.
Article Synopsis
- A 63-year-old woman was investigated for superior vena cava syndrome, resulting in the discovery of a tumor in the azygos vein.
- She underwent video-assisted thoracic surgery to remove the distal end of the vein, followed by complete tumor resection through median sternotomy.
- Two years post-surgery, the patient remains tumor-free and has no complications or graft occlusions in the reconstructed veins, highlighting the effectiveness of thoracoscopic surgery for such tumors.
Article Synopsis
- A 72-year-old woman had a retroperitoneal tumor found during a CT scan, which was 27 mm in size and located away from major blood vessels; imaging suggested it might be a vascular malformation.
- The tumor was removed laparoscopically, and further analysis confirmed it was a capillary arteriovenous malformation, highlighting the challenges in diagnosing such cases before surgery.
The Totten Glacier in East Antarctica, with an ice volume equivalent to >3.5 m of global sea-level rise, is grounded below sea level and, therefore, vulnerable to ocean forcing. Here, we use bathymetric and oceanographic observations from previously unsampled parts of the Totten continental shelf to reveal on-shelf warm water pathways defined by deep topographic features.
View Article and Find Full Text PDFFilGAP, a GAP for Rac1, down-regulates invadopodia formation in breast cancer cells.
Cell Struct Funct
September 2023
Invadopodia are protrusive structures that mediate the extracellular matrix (ECM) degradation required for tumor invasion and metastasis. Rho small GTPases regulate invadopodia formation, but the molecular mechanisms of how Rho small GTPase activities are regulated at the invadopodia remain unclear. Here we have identified FilGAP, a GTPase-activating protein (GAP) for Rac1, as a negative regulator of invadopodia formation in tumor cells.
View Article and Find Full Text PDFArticle Synopsis
- Granulosa cell tumors (GCTs) are a rare type of ovarian cancer that represent around 2% of ovarian malignancies, often linked to irregular bleeding in postmenopausal women and late recurrences following initial treatment.
- In a study, two cases of GCTs were examined to explore the role of serum vascular endothelial growth factor (VEGF) levels as a potential biomarker for treatment effectiveness and recurrence risk.
- The findings suggest that VEGF levels could be clinically significant in monitoring disease progression in GCTs and may help assess the efficacy of treatments like bevacizumab.
Article Synopsis
- COVID-19 can lead to coagulopathy, a condition affecting blood clotting, but the exact mechanisms behind this are still unclear.
- A study in Japan involving 99 hospitalized COVID-19 patients aimed to investigate the relationship between coagulopathy and extracellular vesicle (EV) levels, focusing on various types of EVs derived from different cell types.
- The findings revealed that while no significant differences in EV levels were observed between coagulopathy and non-coagulopathy patients, the levels of CD41+ EVs were significantly higher in patients with coagulopathy compared to healthy volunteers, suggesting a potential role for these EVs in the disease's coagulopathy aspect.
A Case of Fibula Regeneration after Below-the-knee Amputation in an Adult.
Plast Reconstr Surg Glob Open
May 2023
Article Synopsis
- This case report details an adult man who experienced spontaneous regeneration of the fibula after a below-the-knee amputation, despite this phenomenon typically occurring in children.
- The patient had a history of a severe leg injury from a traffic accident, leading to his amputation and subsequent use of a prosthetic limb.
- Radiographic and pathological examinations showed the regenerated fibula was 7 cm long and composed of normal bone tissue, suggesting that factors like preserved periosteum and negative pressure therapy contributed to the regeneration process.
Article Synopsis
- Cancer-associated fibroblasts (CAFs), specifically stromal spindle cells (SSCs), are linked to aggressive tumor behavior in pulmonary adenocarcinomas, influencing development and metastasis.
- A study of 211 surgical patients found SSC-positive cases associated with worse clinicopathological features, such as advanced stage and lymph node metastasis.
- The presence of SSCs in cytological specimens may serve as a crucial indicator for poor prognosis in lung adenocarcinomas, with SSC-positive patients experiencing shorter recurrence-free survival.
Article Synopsis
- A rare anatomical abnormality known as systemic arterial blood supply to a normal lung can lead to pulmonary hypertension, necessitating surgical intervention.* -
- The report details two cases: one involved a woman in her 50s who underwent a left lower lobectomy with embolization support, and another was a man in his 40s who had a left partial resection with advanced imaging techniques.* -
- The study emphasizes the safety and effectiveness of combining interventional radiology with thoracoscopic surgery and cone-beam CT imaging to treat this unusual condition.*
Article Synopsis
- Pulmonary capillary hemangiomatosis (PCH) is a rare lung disease marked by abnormal capillary growth in various lung structures, with no known cause.
- A 38-year-old woman was mistakenly diagnosed with lung carcinoma due to a small nodule, but subsequent surgery revealed that the thickened lung tissue was actually PCH, not cancer.
- The case highlights the need for more research on PCH, as there are only a few documented instances of solitary PCH lesions.
Background/aim: Rho small GTPases regulate cancer cell adhesion, migration and invasion through reorganization of the actin cytoskeleton. Rho GTPase Activating Protein 22 (ARHGAP22) is a Rac-specific GAP and suppresses Rac-dependent lamella formation and cell spreading. We have previously shown that ARHGAP22 localizes at endosomes in human melanoma A7 cells.
View Article and Find Full Text PDFRecent comprehensive analyses of mtDNA and orthogonal RNA-sequencing data revealed that in numerous human cancers, mtDNA copy numbers and mtRNA amounts are significantly reduced, followed by low respiratory gene expression. Under such conditions (called mt-Low), cells encounter severe cell proliferation defects; therefore, they must acquire countermeasures against this fatal disadvantage during malignant transformation. This study elucidated a countermeasure against the mt-Low condition-induced antiproliferative effects in hepatocellular carcinoma (HCC) cells.
View Article and Find Full Text PDFArticle Synopsis
- A young male developed cutaneous IgA vasculitis, hematuria, diarrhea, and pericarditis after his second dose of a COVID-19 mRNA vaccine, showing potential links to autoimmune conditions.
- Despite treatment with anti-inflammatory medications and prednisolone that improved his symptoms, kidney biopsy indicated only minor glomerular changes and no signs of vasculitis.
- This case suggests that COVID-19 vaccination could trigger various autoimmune or inflammatory responses, offering insight into the relationship between these disorders.
Article Synopsis
- The COVID-19 pandemic led to a significant shortage of intravenous anesthetics, particularly impacting patients on extracorporeal membrane oxygenation (ECMO).
- A 52-year-old man with acute respiratory distress syndrome from COVID-19 was treated with ECMO, facing difficulties in managing sedation through traditional IV anesthetics.
- The medical team successfully used inhaled anesthetics delivered through ECMO to reduce the need for intravenous medications, suggesting a potential solution to the shortage issue.
Article Synopsis
- Intracranial dermoid cysts are rare tumors formed from ectodermal cells that don't separate properly during neural tube development, and the case discussed involves a cyst in a 50-year-old man's right temporal lobe.
- Imaging tests, including CT and MRI, helped identify the tumor's characteristics, leading to a differential diagnosis that included similar cysts and tumors before opting for surgical intervention.
- The surgery successfully removed the tumor, which contained hair and keratin, and the patient recovered well without any new neurological issues; however, the case highlighted the importance of monitoring for potential complications, like chemical meningitis, during surgery.
Article Synopsis
- - Patients with severe COVID-19 are vulnerable to secondary infections from multidrug-resistant organisms (MDROs), which can worsen their condition and prolong their ICU stays.
- - A case study of a man in his 60s showed that after struggling with severe COVID-19 pneumonia and requiring mechanical ventilation, he developed multiple infections and needed advanced support (VV-ECMO) over a long period (72 days).
- - The case underscores the difficulties in preventing and treating healthcare-associated infections in critical COVID-19 patients, emphasizing the need for strict infection control and vigilance in monitoring for these infections.
Article Synopsis
- Acute Respiratory Distress Syndrome (ARDS) is a major cause of death in COVID-19 patients, primarily due to a lack of effective treatments.
- The text discusses a combination therapy of etoposide (a chemotherapy drug) and corticosteroids that has shown promising results for five COVID-19 patients with ARDS, all of whom had previous antiviral treatments but continued to deteriorate.
- All patients demonstrated significant improvement in their respiratory symptoms and inflammatory markers after treatment, leading to plans for a larger clinical trial in Japan to further assess this therapy's efficacy and safety.
Article Synopsis
- - Lymphomatoid granulomatosis (LYG) is a rare condition linked to the Epstein-Barr virus that primarily affects the lungs but can also impact other organs such as the skin, liver, and central nervous system, with rare occurrences in the spine.
- - A systematic review identified 15 cases of spinal LYG, showing that the average patient was 43.4 years old, predominantly male, and most had brain lesions alongside spinal involvement; diagnostic methods primarily involved biopsies.
- - The prognosis for spinal LYG is concerning, with a mean follow-up of 21.6 months revealing that 4 out of 15 patients died despite receiving various treatments, indicating a need for more research to understand
Article Synopsis
- * FilGAP, a GTPase-activating protein for Rac, is critical for maintaining this polarity; its overexpression enhances migration speed while its depletion negatively affects cell movement and shape.
- * The interaction of FilGAP with PIP3 and the small GTPase Arf6 is key to regulating cell polarity and migration, highlighting the complex mechanisms that control tumor cell movement.