Notch1 intracellular domain suppresses APP intracellular domain—Tip60–Fe65 complex mediated signaling through physical interaction

AbstractThe amyloid beta-precursor protein (APP) and the Notch receptor are both type 1 integral transmembrane proteins, and both are cleaved by presenilin-dependent gamma-secretase activity. In this study, we have demonstrated that the Notch intracellular domain (Notch1-IC) suppresses APP-intracellular domain (AICD)-mediated ROS generation and cell death after being processed by gamma secretase. Notch1-IC physically interacts with AICD, Fe65, and Tip60, thereby disrupting the association of the AICD–Fe65–Tip60 trimeric transcription activator complex in AICD signaling. AICD–Fe65–Tip60 mediated reactive oxygen species generation was found to be suppressed by Notch1-IC. Furthermore, AICD–Fe65–Tip60 was shown to mediate cell death in human neuroblastoma cells, and the overexpression of Notch1-IC inhibited cell death induced by AICD–Fe65–Tip60. Collectively, our findings indicate that Notch1-IC plays the role of a negative regulator in AICD signaling via the disruption of the AICD–Fe65–Tip60 trimeric complex

Trends in the incidence of cryptorchidism and hypospadias of registry-based data in Korea: a comparison between industrialized areas of petrochemical estates and a non-industrialized area

This study aimed to represent the recent trends in the nationwide incidence of cryptorchidism and hypospadias in Korea, and to determine whether there is evidence of spatial heterogeneity in the incidence. The incidence was calculated as the number of newly diagnosed patients (males) during the first 4 years after a live birth in a population, nationally and regionally (a non-industrialized area (Chuncheon) and petrochemical estates (Yeocheon and Ulsan)), between 2000 and 2005. The data (numerator) for new patients were acquired from the National Health Insurance Review Agency, and the data (denominator) for the resident registration population were from the National Statistical Office. Between 2000 and 2005, the national incidence of cryptorchidism and hypospadias had an increased tendency from 5.01 to 17.43 per 10 000 persons and from 1.40 to 3.28 per 10 000 persons, respectively. The incidence of cryptorchidism was significantly higher in Yeocheon (throughout the study period) and in Ulsan (2001Ulsan ( , 2002Ulsan ( , 2004Ulsan ( and 2005 than the national incidence, whereas the incidence in Chuncheon was significantly lower in 2001 and 2002. It was difficult to compare the rates of hypospadias yearly and regionally because of the small number of cases. In conclusion, the incidence of cryptorchidism has recently increased in Korea. The petrochemical estates, Yeocheon and Ulsan, had a significantly higher incidence of cyptorchidism than the national incidence, which suggests that further study is needed to obtain a more precise estimation of the trends in the incidence of the anomalies and to confirm the association between petrochemicals and the anomalies

Anesthetic management of non-cardiac surgery with adult onset type of cor triatriatum sinister -A case report-

A 45-year-old woman with cor triatriatum sinister was admitted for laparoscopic resection of an ovarian tumor. Her medical history was benign with the exception of a single episode of syncope one year ago. A 1.5-cm membrane fenestration was found on echocardiography, but there were no other cardiac structural anomalies. General anesthesia was established with etomidate, sevoflurane, and remifentanil; no notable events occurred during the anesthesia. As cor triatriatum shows a clinical picture of mitral stenosis (MS), careful anesthetic management is required

Klebsiella pneumoniae Orbital Cellulitis with Extensive Vascular Occlusions in a Patient with Type 2 Diabetes

A 39-year-old woman visited the emergency room complaining of right eye pain and swelling over the preceding three days. The ophthalmologist's examination revealed orbital cellulitis and diabetic retinopathy in the right eye, although the patient had no prior diagnosis of diabetes. It was therefore suspected that she had diabetes and orbital cellulitis, and she was started on multiple antibiotic therapies initially. She then underwent computed tomography scans of the orbit and neck and magnetic resonance imaging of the brain. These studies showed an aggravated orbital cellulitis with abscess formation, associated with venous thrombophlebitis, thrombosis of the internal carotid artery, and mucosal thickening of maxillary sinus with multiple paranasal abscesses. Three days later, initial blood culture grew Klebsiella pneumoniae. She recovered after incision and drainage and antibiotic therapy for 37 days

Central Pontine Myelinolysis in a Patient with Acute Lymphoblastic Leukemia after Hematopoietic Stem Cell Transplantation: A Case Report

We describe a 37-yr-old man who developed central pontine myelinolysis (CPM) after allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After HSCT, desquamation developed on the whole body accompanied by hyperbilirubinemia. The liver biopsy of the patient indicated graft-versus-host disease-related liver disease, and the dose of methylprednisolone was increased. Then, the patient developed altered mentality with eye ball deviation to the left, for which electroencephalogram and magnetic resonance imaging (MRI) scans were done. Brain MRI scan demonstrated the imaging findings consistent with central pontine myelinolysis and extrapontine myelinolysis. He did not have any hyponatremia episode during hospitalization prior to the MRI scan. To the best of our knowledge, presentation of CPM after allogeneic HSCT is extremely rare in cases where patients have not exhibited any episodes of significant hyponatremia. We report a rare case in which hepatic dysfunction due to graft-versus-host disease has a strong association with CPM after HSCT