RESUMEN
Long noncoding RNAs (lncRNAs) interact with other RNAs, DNA and/or proteins to regulate gene expression during development. Erythropoiesis is one developmental process that is tightly controlled throughout life to ensure accurate red blood cell production and oxygen transport to tissues. Thus, homeostasis is critical and maintained by competitive outcomes of pro- and anti-apoptotic pathways. LncRNAs are expressed during blood development; however, specific functions are largely undefined. Here, a culture model of human erythropoiesis revealed that lncRNA Fas-antisense 1 (Fas-AS1 or Saf) was induced during differentiation through the activity of essential erythroid transcription factors GATA-1 and KLF1. Saf was also negatively regulated by NF-κB, where decreasing NF-κB activity levels tracked with increasing transcription of Saf. Furthermore, Saf over-expression in erythroblasts derived from CD34(+) hematopoietic stem/progenitor cells of healthy donors reduced surface levels of Fas and conferred protection against Fas-mediated cell death signals. These studies reveal a novel lncRNA-regulated mechanism that modulates a critical cell death program during human erythropoiesis.
Asunto(s)
Apoptosis , Eritroblastos/citología , Eritrocitos/citología , Eritropoyesis , ARN Largo no Codificante/genética , Receptor fas/genética , Línea Celular Tumoral , Eritroblastos/metabolismo , Eritrocitos/metabolismo , Factor de Transcripción GATA1/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células HEK293 , Humanos , Factores de Transcripción de Tipo Kruppel/metabolismo , Receptor fas/metabolismoRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome in which widespread activation of the immune system causes multi-organ tissue damage. HLH is a serious and potentially fatal disorder characterized by excessive immune system activation. It is characterized by a dysregulation in natural killer (NK) T-cell function, causing activation of lymphocytes and histiocytes. These cells secrete a large number of inflammatory cytokines and infiltrate various tissues causing multi-organ system failure. The spectrum consists of hereditary or "primary" HLH that comprises genetically heterogeneous conditions, occurring during childhood. The secondary form presents later in life and is associated with several conditions mainly malignancy, autoimmune diseases, viral or bacterial infections, and hematological diseases. Here we present an interesting case in which a 39-year-old patient presented with a complaint of shortness of breath. He was diagnosed with obstructive uropathy in the emergency department and subsequently developed acute liver injury, acute kidney injury, Escherichia coli bacteremia, and was diagnosed with HLH with comorbid bacteremia.
RESUMEN
Acute pancreatitis (AP) is a common medical condition with a wide variety of etiologies. One of the common but frequently undetected causes of acute pancreatitis is microlithiasis, which can appear as biliary "sludge" in the gallbladder on imaging. While a broad workup should be initiated, endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the diagnosis of microlithiasis. In this case, we present a severe presentation of acute pancreatitis in a teenager within the postpartum period. A 19-year-old woman presented with severe 10 out of 10 right upper quadrant (RUQ) pain with episodes of nausea that radiated to her back. She had no history of chronic alcoholism, illicit drug use, or over-the-counter supplement use, and no familial history of autoimmune disease, or pancreatitis. The patient was diagnosed with necrotizing acute pancreatitis with gallbladder "sludge" using contrast-enhanced computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP). She followed up with gastroenterology and had a great clinical recovery. Therefore, it is important to consider acute pancreatitis in patients with idiopathic pancreatitis in their postpartum period as they are prone to forming gallbladder "sludge" which can precipitate and cause a variation in gallbladder pancreatitis which can be difficult to detect on imaging.
RESUMEN
Renal tubular acidosis (RTA) refers to a group of disorders in which the elimination of hydrogen ions from the kidney or the reabsorption of filtered bicarbonate is impaired, resulting in metabolic acidosis. Hypokalemia is also prominent in different types of RTA. We are presenting an interesting case about a chronic alcoholic patient who presented to the emergency department and was found to be severely hypokalemic. During her hospital stay, she had multiple cardiac arrests likely secondary to her hypokalemia despite adequate treatment with potassium supplementation. We came to the conclusion of distal RTA in our patient based on hyperchloremic metabolic acidosis, sodium bicarbonate of 10 mmol/L, low potassium, blood urea nitrogen, and creatinine within normal limits, alkaline urine, and a positive urinary anion gap. It is likely that the cause of our patient's underlying type 1 RTA was secondary to her chronic alcohol abuse. Her potassium eventually returned to baseline, and she was discharged.
RESUMEN
Cases of an inguinal bladder hernia (IBH) are rare as the diagnosis may be challenging because patients are often asymptomatic or have nonspecific symptoms. When patients are symptomatic, normally they complain of urinary symptoms. Our patient initially presented to the hospital because he had a ground-level fall after having chest pain while transitioning from a bed to a wheelchair. Incidentally in the emergency department, he was found to have scrotal edema, which was later diagnosed as inguinal bladder herniation. The patient did not have any further episodes of chest pain or abdominal pain once he was given medicinal therapy for his IBH. Surgery is usually the definitive treatment for inguinal bladder herniation, but our patient wished to try medicinal therapy and follow-up outpatient.
RESUMEN
Varicella-zoster virus (VZV) vasculopathy is a granulomatous vasculitis that has a wide variety of clinical presentations. It is most common in patients with HIV not on anti-retroviral therapy (ART) with low cluster of differentiation (CD)4 cell counts. This disease affects the central nervous system and can cause small intracranial bleeds. Our patient presented with stroke-like symptoms in the setting of recent VZV reactivation in the ophthalmic distribution with HIV on ART. Her MRI scan showed a small punctate bleed and the CSF workup was consistent with VZV vasculitis. She was treated with 14 days of acyclovir and five days of high-dose steroids with clinical improvement to baseline.
RESUMEN
This paper describes data related to a research article titled, "Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death" [1]. Long noncoding RNAs (lncRNAs) are increasingly appreciated for their capacity to regulate many steps of gene expression. While recent studies suggest that many lncRNAs are functional, the scope of their actions throughout human biology is largely undefined including human red blood cell development (erythropoiesis). Here we include expression data for 82 lncRNAs during early, intermediate and late stages of human erythropoiesis using a commercial qPCR Array. From these data, we identified lncRNA Fas-antisense 1 (Fas-AS1 or Saf) described in the research article. Also included are 5' untranslated sequences (UTR) for lncRNA Saf with transcription factor target sequences identified. Quantitative RT-PCR data demonstrate relative levels of critical erythroid transcription factors, GATA-1 and KLF1, in K562 human erythroleukemia cells and maturing erythroblasts derived from human CD34(+) cells. End point and quantitative RT-PCR data for cDNA prepared using random hexamers versus oligo(dT)18 revealed that lncRNA Saf is not effectively polyadenylated. Finally, we include flow cytometry histograms demonstrating Fas levels on maturing erythroblasts derived from human CD34(+) cells transduced using mock conditions or with lentivirus particles encoding for Saf.