Quadricuspid aortic valve (QAV) is a very rare congenital abnormality. Here, we present a rare case of QAV incidentally noted in a patient at an advanced age during transthoracic echocardiography (TTE). A 73-yearold man with a history of hypertension, hyperlipidemia, diabetes, and treated prostate cancer was admitted to the hospital with palpitations. An electrocardiogram (ECG) showed T-wave inversion in V5-V6, with initial troponin levels mildly elevated. Acute coronary syndrome was ruled out by serial ECGs that were unchanged, and troponins downtrended. TTE showed a rare and incidental finding of type A QAV with four equal cusps with mild aortic regurgitation.
Neuroendocrine tumors (NETs), which are a rare type of tumor, are defined as epithelial cells with predominantly neuroendocrine differentiation and consist of a spectrum of tumors emerging from stem cells throughout the body and can occur anywhere in the body. While they are rare, the incidence over the past few decades has increased. Here we present a case of a 64-year-old female who was incidentally found to have a duodenal neuroendocrine tumor. The patient initially presented to the emergency department secondary to syncope and collapse. During her trauma evaluation, an incidental lobulated soft tissue mass inferior to the distal stomach was seen on complete computed tomography (CT) scans. The surgery team was consulted for resection of the mass and an octreotide scan was performed prior to resection to further evaluate the mass and to check for any signs of metastatic disease. The octreotide scan demonstrated intense radiotracer accumulation within the duodenal mass consistent with a neuroendocrine tumor and no areas of abnormal radiotracer accumulation suspicious for metastatic disease. Pathology of the resected mass was positive for a well-differentiated neuroendocrine tumor with an organoid pattern and homogenous oval-round neoplastic cells with a salt-pepper nuclear and pseudo glandular arrangement that was wellcircumscribed and partially encapsulated with negative margins. Immunohistochemistry was positive for AE ⅓, CD56, Synaptophysin, and chromogranin and negative for CD117, DOG-1, CD34, and CD45. The prevalence of NETs has increased over the years due to the improvement in diagnostic tools, such as upper gastrointestinal endoscopy. In addition to the fact that the duodenum is a rare location for such tumors, neuroendocrine tumors are also typically found in those under 50 years old. However, our patient was found to have both a duodenal mass and was over the age of 50 at the time of presentation and diagnosis. To date, a consensus on a conclusive treatment of duodenal NETs (D-NETs) has not been reached. This case brings to light the importance of further research in diagnosing and treating neuroendocrine tumors and also raises awareness for clinicians to have this in their differential.
Mixed lineage leukemia (MLL) is an aggressive blood cancer that results from genetic alterations in the MLL1 gene. This gene encodes an enzyme that methylates histone H3 on lysine 4 (H3K4) as a part of the MLL1 multi-protein complex. MLL-related genetic alterations create fusion proteins that render MLL1 incapable of its methyltransferase activity, with particularly devastating effects at homeobox genes. Problematically, higher eukaryotes contain many functionally redundant complexes that complicate the study of MLL1 and associated cancers in a living system. Moreover, the translocations that lead to the formation of MLL1 fusion proteins are variable, generating similarly variable fusion proteins. This inconsistency further complicates the use of MLL1 as a drug target. However, several accessory proteins within the complex are required for catalytic activity, and present possible drug targets themselves. Herein we present an in vivo system for the study of the MLL1 complex in Saccharomyces cerevisiae, making use of the homologous Set1/COMPASS complex. We genetically replaced COMPASS members from S. cerevisiae with their human homologs using antibiotic resistance cassettes, and subsequently performed phenotypic characterization of chimeric COMPASS/MLL1 complexes, assessing global H3K4 methylation status. Selected chimeric yeast-human methyltransferase complexes conferred catalytic activity at varying degrees, while others did not confer methyltransferase activity. Notably, we observed H3K4 dimethylation levels comparable to wild type when human Ash2L replaced yeast Bre2 but reduced levels of H3K4 trimethylation with this same chimeric complex. Together, these data represent a proof of concept for simplifying the study of this clinically important protein complex in a tractable in vivo system, and also offer mechanistic insight into the functional role of a catalytically essential accessory protein within the MLL1 complex through our model.
Genomic rearrangements involving the MLL1 gene are prevalent in human cancers, especially mixed lineage leukemia. This gene encodes an enzyme that methylates histone H3 on lysine 4 (H3K4) as a part of the MLL1 multi‐protein complex. The MLL1 complex regulates the expression of many genes via this epigenetic mark, including homeobox genes. Problematically, higher eukaryotes contain many functionally redundant complexes that complicate the study of MLL1 and associated cancers in a living system. Furthermore, due to the nature of the disease‐causing mutations, namely chromosomal rearrangements, MLL1 is not a promising drug target. However, several accessory proteins within the complex are required for catalytic activity, presenting possible drug targets themselves. Herein we present an in vivo system for the study of the MLL1 complex in Saccharomyces cerevisiae, making use of the homologous Set1/COMPASS complex. We genetically replaced COMPASS members from S. cerevisiae with their human homologs using antibiotic resistance cassettes. We then performed phenotypic characterization of chimeric COMPASS/MLL1 complexes assessing global H3K4 methylation status. Selected chimeric yeast‐human methyltransferase complexes conferred catalytic activity at varying degrees, while others did not confer methyltransferase activity. Notably, we observed H3K4 dimethylation levels comparable to wild type when human Ash2L replaced yeast Bre2 but reduced levels of H3K4 trimethylation with this same chimeric complex. Together, these data represent a proof of concept for simplifying the study of this clinically important protein complex in a tractable in vivo system, and also offer mechanistic insight into the functional role of a catalytically essential accessory protein within the MLL1 complex.Support or Funding InformationThis research was supported by grants from the National Center for Research Resources (5 P20 RR016461) and the National Institute of General Medical Sciences (8 P20 GM103499) from the National Institutes of Health.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Patent foramen ovale (PFO) is a congenital heart anomaly with persistent non-closure of the atrial septum that generally closes six to 12 months after birth in the majority of adults. While remaining asymptomatic in the majority of cases, PFO could lead to paradoxical embolism and cryptogenic strokes in most symptomatic cases. The incidence of small arterial occlusion due to paradoxical emboli is quite uncommon. In this report, we present a case of a 51-year-old man who presented with acute left-sided painless visual loss due to central retinal artery occlusion (CRAO). Stroke work-up and hypercoagulability evaluations were negative. The patient was found to have PFO with the initial presentation as CRAO, a rather rare presentation in the setting of PFO. In this report also, we discuss the clinical presentation, pathogenesis, and the current evidence-based therapeutic options in the management of PFO in adults, highlighting the importance of considering this diagnostic entity in the setting of acute visual loss, as with our case presentation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.