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A structural protein of SARS-CoV-2, nucleocapsid (N) protein is abundantly expressed during viral replication. The N protein is phosphorylated by glycogen synthase kinase (GSK)-3 on the serine/arginine (SR) rich motif located in disordered regions. Although phosphorylation by GSK-3{beta} constitutes a critical event for viral replication, the molecular mechanism underlying N phosphorylation is not well understood. In this study, we found the putative alpha-helix L/FxxxL/AxxRL motif known as the GSK-3 interacting domain (GID), commonly found in many endogenous GSK-3{beta} binding proteins, such as Axins, FRATs, WWOX and GSKIP. Indeed, N interacts with GSK-3{beta} similarly to Axin, and Leu to Glu substitution of the GID abolished the interaction, with loss of N phosphorylation. Unlike with endogenous GID proteins, the N interaction neither disturbs endogenous GSK-3 activity nor regulates subsequent canonical Wnt activity and the Snail-EMT program. Notably, N abundance in SARS-CoV-2 is incomparably high compared to other coronaviruses, such as 229E, OC43 and HKU1. Compared to other coronaviruses, N harbors a CDK1 primed phosphorylation site and Gly-rich linker for enhanced phosphorylation by GSK-3{beta}. Furthermore, we found that the S202R mutant found in Delta and R203K/G204R mutant found in the Omicron variant allows increased abundance and hyper-phosphorylation of N. Our observations suggest that the emergence of GID and mutations for increased phosphorylation in N may have contributed to the emergence of SARS-CoV-2 and evolution of variants, respectively. Further study, especially in a BSL3-equipped facility, is required to elucidate the functional importance of GID and N phosphorylation in SARS-CoV-2 and variants.
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OBJECTIVES: This study was designed to analyze biomarker-related publications and patent trends which biobanks could consider in planning biosample collections for biomarker research. METHODS: Publications and patents containing the term “biomarker” in the title published between 1998 to 2017 were retrieved using Scopus database and Google Patents search engine. RESULTS: Over the last 20 years there has been a steady increase in biomarker-related publications and patents; however this has slowed for patents over the last few years. Publications in 2017 that contained blood, serum, and plasma search terms in the abstract accounted for 50%, and serum as a search term in the title and abstract was more numerous than those containing blood, plasma, tissue, or urine. Blood-related patents were the most common patent in the last 10 years, and accounted for 110 patents in 2017. Biomarker-related publications since 2010 containing RNA and protein search terms in the title and abstract, were more numerous than those containing DNA and metabolite search terms. More than 27% of biomarker-related publications in 2017 and 21% of biomarker-related patents were associated with cancer. CONCLUSION: The results of this study will help biobanks establish a biosample collection strategy for clinical application.
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Biomarcadores , ADN , Plasma , Publicaciones , ARN , Motor de BúsquedaRESUMEN
Familial Mediterranean fever (FMF) is an inherited autosomal recessive disorder, ethnically restricted and commonly found among populations surrounding the Mediterranean Sea. FMF is the most prevalent autoinflammatory disease; is characterized by recurrent, self-limited episodes of fever with serositis; and is caused by Mediterranean fever gene (MEFV) mutations on chromosome 16. We describe a case of adult-onset FMF with complete symptomatic remission during pregnancy, without the use of colchicine. A 25-year-old woman had presented with periodic fever, abdominal pain, and vomiting since she was 21. Her abdominal computed tomography scan showed intestinal nonrotation. She underwent exploratory laparotomy and appendectomy for her symptoms 1 year prior. She had a symptom-free pregnancy period, but abdominal pain and fever recurred after delivery. Mutation analysis of the MEFV gene revealed two point mutations (p.Leu110Pro and p.Glu148Gln). We report an adult female patient with FMF in Korea with complete symptomatic remission during pregnancy.
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Adulto , Femenino , Humanos , Embarazo , Dolor Abdominal , Apendicectomía , Cromosomas Humanos Par 16 , Colchicina , Fiebre Mediterránea Familiar , Fiebre , Corea (Geográfico) , Laparotomía , Mar Mediterráneo , Mutación Puntual , Serositis , VómitosRESUMEN
Eosinophilic cholecystitis (EC) is a rare form of acute cholecystitis, of which diagnosis is based on classical symptoms of cholecystitis with a presence of >90% eosinophilic infiltration within the gall bladder. EC rarely manifests in idiopathic hypereosinophilic syndrome (IHES). Here, we report two cases of EC with IHES. One is a 57-year-old male who presented with acute right upper quadrant (RUQ) pain, jaundice and fever. The initial peripheral blood eosinophil count was 2,070/mm3, and further elevated to 12,590/mm3. Acute acalculous cholecystitis with cholangitis was confirmed by computed tomography (CT). He improved with endocopic nasobiliary drainage and antibiotic therapy. The other is a 64-year-old female who presented with acute RUQ pain. She also complained of dyspnea and tingling sensation of both hands and feet. The initial peripheral blood eosinophil count was 10,400/mm3. Abdominal CT revealed findings suggestive of acute acalculous cholecystitis. She improved with systemic glucocorticosteroid therapy. No other causes of hypereosinophilia were found in either patients. Thus, cholecystectomy may not be mandatory for the treatment of EC with IHES.
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Femenino , Humanos , Masculino , Persona de Mediana Edad , Colecistitis Alitiásica , Colangitis , Colecistectomía , Colecistitis , Colecistitis Aguda , Diagnóstico , Drenaje , Disnea , Eosinófilos , Fiebre , Pie , Mano , Síndrome Hipereosinofílico , Ictericia , Sensación , Tomografía Computarizada por Rayos X , Vejiga UrinariaRESUMEN
The occurrence of valporic acid (VPA)-induced pancreatitis is a rare condition, predominantly observed in adolescent. Also, the occurrence of VPA-associated with hemorrhagic pseudocyst is extremely rare. We report the case of a 54-year-old man who had been taking VPA for uncontrolled seizures. He was admitted to our hospital with complaints of abdominal pain and diagnosed with acute on chronic pancreatitis. There were no other causes explaining pancreatitis, and it was thought to be due to VPA therapy. Despite of cessation of VPA, there was ongoing severe abdominal pain with fever. The patient underwent follow-up CT, which revealed a large loculated fluid collection that was observed with intra-cystic hemorrhage. After treatment with percutaneous catheter drainage, he was discharged with regression of the pancreatic pseudocyst. VPA-associated pancreatitis with hemorrhagic pseudocyst is rare but possible. Therefore, this possibility should be considered in the cause of hemorrhagic pseudocyst in a patient taking VPA.
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Adolescente , Humanos , Persona de Mediana Edad , Dolor Abdominal , Catéteres , Drenaje , Fiebre , Estudios de Seguimiento , Hemorragia , Seudoquiste Pancreático , Pancreatitis , Pancreatitis Crónica , Convulsiones , Ácido ValproicoRESUMEN
Stenotrophomonas maltophilia is an ubiquitous aerobic Gram-negative bacillus. Hospitalization and prior antibiotic therapy are risk factors for S. maltophilia infection. This organism is isolated with increasing frequency from hospitalized patients and may cause therapeutic problems because of its intrinsic resistance to common antibiotics and the immunodeficiency status of the affected host. S. maltophilia has been reported to be commonly associated with pneumonia and urinary tract infection. However, biliary infection caused by S. maltophilia is very rare. Herein, we report on a case of acute cholecystitis that developed secondary to S. maltophilia bacteremia in a patient with hepatitis-B related liver cirrhosis and gallbladder stone.
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Humanos , Antibacterianos , Bacillus , Bacteriemia , Colecistitis Aguda , Vesícula Biliar , Hospitalización , Cirrosis Hepática , Neumonía , Factores de Riesgo , Stenotrophomonas maltophilia , Infecciones UrinariasRESUMEN
OBJECTIVE: To investigate the influence of laparoscopic surgery on the natural conception rate in infertile women with endometriosis during the first year after the operation. METHODS: We retrospectively studied 43 infertile women with surgically proven endometriosis. The natural conception rate was investigated for the 12 months after the laparoscopy. RESULTS: The overall pregnancy rate was 41.9% (18/43). 66.7% (12/18) and 94.4% (17/18) of the patients conceived within postoperative 3 months and 6 months, respectively. The spontaneous pregnancy rate was not associated with the severity of endometriosis or laparoscopic findings or the type of surgery. The pregnancy rate for stage IV was relatively low (20.0%) compared to stage I, II, and III (35.7%, 44.4%, and 53.3%, respectively), although it did not reach statistical significance. CONCLUSION: Conservative surgical treatment with laparoscopy and a prompt attempt at natural conception may be effective for infertile patients with endometriosis.
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Femenino , Humanos , Endometriosis , Fertilización , Infertilidad , Laparoscopía , Índice de Embarazo , Estudios RetrospectivosRESUMEN
A 73-year-old, previously healthy man presented with nausea, vomiting, diarrhea, dry mouth and febrile sensation 3 hours after eating boiled wild mushrooms. After admission, he showed progressive severe respiratory distress, pancytopenia, azotemia, hypotension, hypoxemia and consolidation of the entire left lung on chest radiography. With a preliminary diagnosis of necrotizing pneumonia, he underwent left pneumonectomy in order to remove all necrotic lung tissue. Lung histology showed extensive hemorrhagic necrosis, massive inflammatory cell infiltration, prominent proliferation of young fibroblasts and the formation of an early-stage hyaline membrane along the alveolar wall. Despite aggressive treatment, including mechanical ventilation, continuous renal replacement therapy and administration of granulocyte colony stimulating factor and broad spectrum antibiotics, he died on hospitalization day 13. Subsequently, the mushroom was identified as Podostroma cornu-damae. This is the first case of a histological evidence of lung involvement by Podostroma cornu-damae poisoning in Korea.
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Anciano , Humanos , Agaricales , Hipoxia , Antibacterianos , Azotemia , Factores Estimulantes de Colonias , Diagnóstico , Diarrea , Ingestión de Alimentos , Fibroblastos , Granulocitos , Hospitalización , Hialina , Hipotensión , Corea (Geográfico) , Pulmón , Membranas , Boca , Intoxicación por Setas , Náusea , Necrosis , Pancitopenia , Neumonectomía , Neumonía , Intoxicación , Radiografía , Terapia de Reemplazo Renal , Respiración Artificial , Insuficiencia Respiratoria , Sensación , Tórax , VómitosRESUMEN
Henoch-Schonlein purpura (HSP) is common in childhood and often self-limiting. There have been limited studies on elderly-onset HSP nephritis (HSPN). A 76-yr-old man was transferred to our hospital with a 1-month history of oliguria, abdominal pain, edema and palpable purpura in the legs. Three months ago, he was admitted to another hospital with jaundice, and consequently diagnosed with early common bile duct cancer. The patient underwent a Whipple's operation. Antibiotics were administrated because of leakage in the suture from the surgery. However, he showed progressive renal failure with edema and purpura in the legs. Laboratory investigations showed serum creatinine 6.4 mg/dL, 24-hr urine protein 8,141 mg/day, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) 1:40 and C3 below 64.89 mg/dL. Renal biopsy showed crescentic glomerulonephritis, as well as mesangial and extracapillary Ig A deposition. We started steroid therapy and hemodialysis, but he progressed to end-stage renal failure and he has been under maintenance hemodialysis. We describe elderly onset HSPN with MPO-ANCA can be crescentic glomerulonephritis rapidly progressed to end stage renal failure.
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Anciano , Humanos , Masculino , Anticuerpos Anticitoplasma de Neutrófilos/análisis , Neoplasias del Conducto Colédoco/complicaciones , Complemento C3/análisis , Creatinina/sangre , Edema/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Glomerulonefritis/patología , Vasculitis por IgA/diagnóstico , Diálisis Renal , Insuficiencia Renal/etiología , Esteroides/uso terapéuticoRESUMEN
OBJECTIVE: In 2009 anti-Mullerian hormone (AMH) assay was approved for clinical use in Korea. This study was performed to determine the reference values of AMH for predicting ovarian response to controlled ovarian hyperstimulation (COH) using the clinical assay data. METHODS: One hundred sixty-two women who underwent COH cycles were included in this study. We collected data on age, basal AMH and FSH levels, total dose of gonadotropins, stimulation duration, and numbers of oocytes retrieved and fertilized. Blood samples were obtained on cycle day 3 before gonadotropin administration started. Serum AMH levels were measured at a centralized clinical laboratory center. The correlation between the AMH level and COH outcomes and cut-off values for poor and high response after COH was analyzed. RESULTS: Concentration of AMH was significantly correlated with the number of oocytes retrieved (OPU; r=0.700, p or =20) response were 0.94+/-0.15 ng/mL, 2.79+/-0.21 ng/mL, and 6.94+/-0.90 ng/mL, respectively. The cut-off level, sensitivity and specificity for poor and high response were 1.08 ng/mL, 85.8%, and 78.6%; and 3.57 ng/mL, 94.4%, and 83.3%, respectively. CONCLUSION: Our data present clinical reference values of the serum AMH level for ovarian response in Korean women. The serum AMH level could be a clinically useful predictor of ovarian response to COH.
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Femenino , Humanos , Hormona Antimülleriana , Gonadotropinas , Corea (Geográfico) , Oocitos , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: During stimulated IVF cycles, up to 15% of oocytes are recovered as immature. The purpose of this study was to investigate the trend of oocyte maturity in repeated ovarian stimulation for IVF. METHODS: One hundred forty-eight patients were selected who underwent two consecutive IVF cycles using same stimulation protocol during 2008 to 2010. Ovarian stimulation was performed with FSH and human menopausal gonadotropin and flexible GnRH antagonist protocol in both cycles. Oocyte maturity was assessed according to presence of germinal vesicle (GV) and the first polar body. Immature oocyte was defined as GV stage or metaphase I oocyte (GV breakdown with no visible polar body) and cultured up to 48 hours. If matured, they were fertilized with ICSI. RESULTS: Percentages of immature oocytes were 30.8% and 32.9% (p=0.466) and IVM rates of immature oocytes were 36.2% and 25.7% (p=0.077), respectively. A significant correlation was noted between percentage of immature oocytes in the two cycles (R=0.178, p=0.03). Women with >40% immaturity in both cycles (n=21) showed lower fertilization rate of in vivo matured oocytes (56.4% vs. 72.0%, p=0.005) and lower pregnancy rate (19.0% vs. 27.1%, p=0.454) after the second cycle when compared with women with <40% immaturity (n=70). In both groups, female age, number of total retrieved oocyte and embryos transferred were similar. CONCLUSION: In repeated ovarian stimulation cycles for IVF, the immature oocyte tended to be retrieved repetitively in consecutive IVF cycles.
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Femenino , Humanos , Estructuras Embrionarias , Fertilización , Hormona Liberadora de Gonadotropina , Gonadotropinas , Metafase , Oocitos , Inducción de la Ovulación , Cuerpos Polares , Índice de EmbarazoRESUMEN
The Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) is one of the major genomic resources for human genetics and immunological studies. Use of LCLs is currently extended to pharmacogenetic studies to investigate variations in human gene expression as well as drug responses between individuals. We evaluated four common internal controls for gene expression analysis of selected hematopoietic transcriptional regulatory genes between B cells and LCLs. In this study, the expression pattern analyses showed that TBP (TATA box-binding protein) is a suitable internal control for normalization, whereas GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is not a good internal control for gene expression analyses of hematopoiesis-related genes between B cells and LCLs at different subculture passages. Using the TBP normalizer, we found significant gene expression changes in selected hematopoietic transcriptional regulatory genes (downregulation of RUNX1 , RUNX3 , CBFB , TLE1, and NOTCH2; upregulation of MSC and PLAGL2) between B cells and LCLs at different passage numbers. These results suggest that these hematopoietic transcriptional regulatory genes are potential cellular targets of EBV infection, contributing to EBV-mediated B-cell transformation and LCL immortalization.
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Humanos , Linfocitos B , Línea Celular , Infecciones por Virus de Epstein-Barr , Expresión Génica , Genes Reguladores , Genética Médica , Organofosfatos , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia ArribaRESUMEN
Intestinal lymphangiectasia (IL) is a rare disorder, characterized by dilatation of intestinal lymphatics and leakage from ruptured lacteals to the intestinal lumen. Primary IL may be due to a congenital malformation of the lymphatic system, whereas secondary IL is caused by decreased lymph flow from thoracic ductsdue to elevated left subclavian vein pressure as a result of a preceding inflammatory or neoplastic disease. IL can present as protein-losing enteropathy with clinical manifestations of hypoproteinemia, hypoalbuminemia, edema, ascites, or pleural effusions. In very rare cases, it can present as severe intestinal bleeding. We experienced a 48-year-old woman presenting with recurring hematochezia and melena. She was diagnosed bydouble balloon enteroscopy, and surgical resection was needed to stop bleeding. In conclusion, IL can present clinically as painless chronic blood loss. If IL is locally distributed, surgical resection may be needed to control bleeding and to exclude other underlying causes in some patients.
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Femenino , Humanos , Persona de Mediana Edad , Ascitis , Dilatación , Enteroscopía de Doble Balón , Edema , Hemorragia Gastrointestinal , Hemorragia , Hipoalbuminemia , Hipoproteinemia , Sistema Linfático , Melena , Derrame Pleural , Enteropatías Perdedoras de Proteínas , Vena SubclaviaRESUMEN
Tuberculosis is an opportunistic infection that causes significant morbidity and mortality in recipients of renal transplants. Although tuberculous peritonitis is easily diagnosed by paracentesis, it is difficult to diagnosis in the absence of ascites. Laparotomy and laparoscopic biopsies are needed for the diagnosis of tuberculous peritonitis. According to recent reports, the latter has a better outcome because of fewer associated complications. A case of tuberculous peritonitis in a renal transplant patient is reported that was diagnosed by laparoscopic peritoneal biopsy
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Humanos , Ascitis , Biopsia , Trasplante de Riñón , Laparotomía , Infecciones Oportunistas , Paracentesis , Peritonitis Tuberculosa , Diálisis Renal , Trasplantes , TuberculosisRESUMEN
BACKGROUND AND OBJECTIVES: The correlation between brain natruretic peptide (BNP) level and cardiac autonomic function has been studied in type 2 diabetic patients. However, there is limited data from patients with normal systolic function. We evaluated the association between heart rate recovery (HRR) representing autonomic dysfunction and three plasma BNP levels: pre-exercise, post-exercise, and change during exercise in patients with normal systolic function. SUBJECTS AND METHODS: Subjects included 105 patients with chest pain and normal systolic function. HRR was defined as the difference between the peak heart rate and the rate measured two minutes after completion of a treadmill exercise test. We measured plasma BNP levels before exercise, 5 minutes after completion of exercise, and during exercise (absolute value of difference between pre- and post-exercise BNP levels). RESULTS: Patients with abnormal HRR values (< or =24 beats for the first 2 minutes of HRR) had lower high-density lipoprotein, lower peak heart rates, and higher pre- and post-exercise BNP levels than patients with normal HRR values. The patients with coronary artery disease (CAD) had abnormal HRR. However, no significant differences were found between the two groups in terms of history of hypertension (HTN), diabetes, and peak systolic blood pressure (SBP) and diastolic blood pressure (DBP). HRR was significantly associated with pre-exercise BNP (r=-0.36, p=0.004) and post-exercise BNP (r=-0.27, p=0.006), but not BNP changes. Further, pre-exercise BNP levels showed a greater association with HRR than post-exercise BNP levels. CONCLUSION: HRR is independently associated with pre-exercise and post-exercise BNP levels, even in patients with normal systolic function.
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Humanos , Presión Sanguínea , Encéfalo , Dolor en el Pecho , Enfermedad de la Arteria Coronaria , Prueba de Esfuerzo , Corazón , Frecuencia Cardíaca , Hipertensión , Lipoproteínas , Plasma , Volumen Sistólico , TóraxRESUMEN
BACKGROUND AND OBJECTIVES: A distortion product otoacoustic emission (DPOAE) is a non-invasive method which is commonly used to assess the hearing function of the cochlea and to reflect objective information of specific frequency in the cochlea. We hypothesize that after applying a broad band noise (BBN), the outer hair cell's function will change and cause reduction in the amplitude of DPOAEs and signal to noise ratio (SNR). SUBJECTS AND METHOD: We performed the examination on 40 subjects (80 ears) who have a normal hearing function. DPOAEs were recorded before and after BBN stimulation (intensity: 90 dB HL, duration: 10 minutes). RESULTS: After the BBN stimulation, the amplitude of DPOAEs and SNR were decreased at all frequencies. The amplitude of DPOAEs and SNR decreased 0.3-1.6 dB SPL, 0.6-1.5 dB SPL, respectively. Decreases in the amplitude had statistical significances after 3 and 6 minutes in 1 kHz, 3 and 6 minutes in 2 kHz, immediately after noise exposure, and after 3 and 6 minutes in 6 kHz. However, the SNR changes had statistical significance only after 3 minutes in 1 kHz. After the stimulation, pure tone threshold at 4 kHz increased 3.2+/-3.9 dB HL. After the BBN exposure, the amplitude of DPOAEs and SNR decreased at all frequencies and most of them recovered within 12 minutes. CONCLUSION: These results suggest that DPOAE could be a clinically useful method for the purpose of screening, managing and assessing the prognosis of acoustic trauma and noise induced sensorineural hearing loss.
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Fatiga Auditiva , Cóclea , Cabello , Audición , Pérdida Auditiva Provocada por Ruido , Pérdida Auditiva Sensorineural , Tamizaje Masivo , Ruido , Pronóstico , Relación Señal-RuidoRESUMEN
BACKGROUND/AIMS: The clinical usefulness of nasogastric tube insertion in poisoning patients is controversial. This study compared the incidence of aspiration pneumonia between patients with or without nasogastric tubes. METHODS: We retrospectively reviewed the clinical reports of poisoning patients seen from January 2006 to December 2007. We classified the patients into groups with and without nasogastric tube insertion and evaluated the incidence and risk factors of aspiration pneumonia. RESULTS: Ultimately, 63 patients were included. The incidence of aspiration pneumonia was higher in patients with nasogastric tube insertion than in patients without nasogastric tube insertion (conscious patients: 58.8% vs. 11.8%, p=0.010; unconscious patients: 72.2% vs. 27.3%, p=0.027). Nasogastric tube insertion was a significant risk factor for developing aspiration pneumonia (odds ratio 3.54; 95% confidence interval 1.74~12.34). CONCLUSIONS: Nasogastric tube insertion did not prevent aspiration pneumonia, but was a risk factor. The results have implications in the development of a hypothesis about why a nasogastric tube increases the risk of aspiration pneumonia. This study has important limitations stemming mostly from other compounding factors and its retrospective design.
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Humanos , Carbón Orgánico , Incidencia , Neumonía por Aspiración , Estudios Retrospectivos , Factores de Riesgo , Inconsciente en PsicologíaRESUMEN
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide1). Extrahepatic metastasis of HCC is now increasing due to prolonged survival. Most extrahepatic HCC occurs in patients with advanced stages. The lung, abdominal lymph nodes, and bone are common sites of extrahepatic metastasis. However, the parathyroid gland has not been reported as a metastatic focus. We report the first case of parathyroid metastasis as the first single metastasis site of HCC and microscopic tumor-to-tumor metastasis to a parathyroid adenoma.