β1- and β2-adrenergic receptors (ARs) regulate cardiac contractility, calcium handling and protein phosphorylation. The present study aimed to examine the expression levels of vascular endothelial ...growth factor A (VEGF‑A) and several G proteins, and the phosphorylation of transcription factor GATA binding protein 4 (GATA4), by western blot analysis, using isolated hearts from 6 month‑old transgenic (TG) mice that overexpress β1AR or β2AR. Cardiac contractility/relaxation and heart rate was increased in both β1AR TG and β2AR TG mouse hearts compared with wild type; however, no significant differences were observed between the β1‑ and β2AR TG mouse hearts. Protein expression levels of inhibitory guanine nucleotide‑binding protein (Gi) 2, Gi3 and G‑protein‑coupled receptor kinase 2 were upregulated in both TG mice, although the upregulation of Gi2 was more prominent in the β2AR TG mice. VEGF‑A expression levels were also increased in both TG mice, and were highest in the β1AR TG mice. In addition, the levels of phosphorylated‑GATA4 expression were increased in β1‑ and β2AR TG mice. In conclusion, the present study demonstrated that cardiac contractility/relaxation and heart rate is increased in β1AR TG and β2AR TG mice, and indicated that this increase may be related to the overexpression of G proteins and G‑protein‑associated proteins.
Left ventricular hypertrophy (LVH) refers to the expansion and the enlarged myocardium due to the increased resistance to ejection from the left ventricle to the aorta and/or the periphery, or the ...long-term burden imposed by the blood increase. Hypertension is a major risk factor that accounts for more than 50% of the causes of cardiovascular disease. If hypertension endure in the long term, the myocardium responds to abnormal heartbeat in the heart. Therefore, the prevalence of left ventricular hypertrophy also increases. As a result of genome-wide association study (GWAS) analysis for European people, PDGFC, MARK3, and BCL2 were related to blood pressures. In this study, the genetic polymorphisms of PDGFC, MARK3, and BCL2 were extracted and selected based on Korean genomic and epidemiologic data, and then logistic regression analysis was performed on LVH. As a result, one SNP (rs9307953) in PDGFC gene, four SNPs (rs6575983, rs17679475, rs2273703 and rs10141388) in MARK3 gene and two SNPs (rs17756073 and rs17070739) in BCL2 gene were statistically significant. The rs6575983 of the MARK3 gene showed the highest significance level ($P=7.2{\times}10^{-3}$) among the SNPs and the relative risk of 1.08 (95% confidence interval: 1.06 to 1.45). These results suggest that the polymorphisms of PDGFC, MARK3, and BCL2 not only affect European blood pressures but also correlate with LVH in Korean. These results suggest that increased understanding of the genetic correlations of the pathogenesis of LVH.
The UL112-113 region of the human cytomegalovirus (HCMV) genome encodes four phosphoproteins of 34, 43, 50, and 84 kDa that promote viral DNA replication. Co-transfection assays have demonstrated ...that self-interaction of these proteins via the shared N-termini is necessary for their intranuclear distribution as foci and for the efficient relocation of a viral DNA polymerase processivity factor (UL44) to the viral replication sites. However, the requirement of UL112-113 N-terminal residues for viral growth and DNA replication has not been fully elucidated. Here, we investigated the effect of deletion of the N-terminal regions of UL112-113 proteins on viral growth and oriLyt-dependent DNA replication. A deletion of the entire UL112 region or the region encoding the 25 N-terminal amino-acid residues from the HCMV (Towne strain) bacmid impaired viral growth in bacmid-transfected human fibroblast cells, indicating their requirement for viral growth. In co-immunoprecipitation assays using the genomic gene expressing the four UL112-113 proteins together, the 25 N-terminal amino-acid residues were found to be necessary for stable expression of UL112-113 proteins and their self-interaction. These residues were also required for efficient binding to and relocation of UL44, but not for interaction with IE2, an origin-binding transcription factor. In co-transfection/replication assays, replication of the oriLyt-containing plasmid was promoted by expression of intact UL112-113 proteins, but not by the expression of 25-amino-acid residue-deleted proteins. Our results demonstrate that the 25 N-terminal amino-acid residues of UL112-113 proteins that mediate self-interaction contribute to viral growth by promoting their binding to UL44 and the initiation of oriLyt-dependent DNA replication.
Recently, many studies have investigated the role of extracellular vesicles (EVs) on reproductive events, including embryo development and death, oviduct–embryo crosstalk, in vitro fertilization and ...others. The aim of this study was to demonstrate whether outgrowth embryo–derived EVs function as bioactive molecules and regulate mouse embryonic developmental competence in vitro and implantation potential in utero. The EVs from mouse outgrowth embryos on 7.5 days postcoitum were detected and selectively isolated to evaluate the embryotrophic functions on preimplantation embryos. Developmental outcomes such as the percentage of blastocyst formation, hatching, and trophoblastic outgrowth were assessed. Furthermore, the total cell number and apoptotic index of blastocysts, which were incubated with EVs during the culture period, were evaluated by fluorescence microscopy. Implantation potential in utero was investigated following embryo transfer. The EVs from outgrowth embryo–conditioned media have rounded membrane structures that range in diameter from 20 to 225 nm. Incubation with EVs improved preimplantation embryonic development by increasing cell proliferation and decreasing apoptosis in blastocysts. Moreover, the implantation rates following embryo transfer were significantly higher in EV–supplemented embryos compared with the control. Collectively, EVs from outgrowth embryo could enhance the embryonic developmental competence and even implantation potential in mice.
Extracellular vesicles (EVs) participate in intercellular communication, however, its embryotrophic effect is still unclear. Outgrowth embryo–derived EVs as bioactive molecules improves the mouse embryonic developmental competence in vitro and implantation potential in utero.
We investigated the effects of weekend admission on adverse cardiac events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Patients with NSTE-ACS treated with ...percutaneous coronary intervention (PCI) were divided into a "weekend group" and a "weekday group" according to the emergency room arrival time. The primary outcome was 30-day major adverse cardiac events (MACE) including cardiac death, recurrent myocardial infarction, repeat revascularization, and urgent PCI. Of 577 patients, 168 patients were allocated to the weekend and 409 patients to the weekday group. The incidence of 30-day MACE was significantly higher in the weekend group (Crude: 15.5% vs. 7.3%, P = 0.005; propensity score matched: 12.8% vs. 4.8%, P = 0.041). After adjustment for all the possible confounding factors, in Cox proportional hazard regression analysis, weekend admission was associated with a 2.1-fold increased hazard for MACE (HR, 2.13; 95% CI, 1.26-3.60, P = 0.005). These findings indicate that weekend admission of patients with NSTE-ACS is associated with an increase in 30-day adverse cardiac event.
The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following ...transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1)-immunoreactive microvessels in their ischemic hippocampal CA1 region.
Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry.
About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion.
CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults.
This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) ...patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS).
We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV).
In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively.
Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.
2019년 12월, 중국 후베이성 우한시에서 COVID-19환자가 처음으로 보고되었다. 그 이후 국내에서 신종 코로나 바이러스에 의해 야기된 중증 급성 호흡기 증후군 환자가 급격하게 증가하였다. 이러한 새로운 변종 바이러스는 기침, 인후통, 비루, 호흡곤란, 폐렴 및 기타 폐질환을 유발한다. 중증 급성 호흡기 증후군 코로나 바이러스 2는 RNA바이러스로, ...실시간 역전사효소중합효소 연쇄반응을 통한 분자진단 검사가 COVID-19의 진단에 폭 넓게 사용되고 있다. 국내 질병관리본부와 식품의약품 안전처의 긴급 사용 허가 승인에 따라, 건강한 사람과 COVID-19 환자로부터 검체를 채취하여 진단검사의학적인 방법을 통해 진단을 수행하고 있다. 기존에 출판된 많은 문헌 고찰을 통해, 본 연구에서는 역학, 증상 및 질병관리본부의 승인을 받은 현재의 검사실 내 COVID-19 분자 진단 방법, 분자 진단 검사와 혈청학적 진단의 차이, 임상 검체 가이드라인 등을 다시 한 번 확인하고자 하였다. 추가적으로 본 연구를 통해 국내 의료기관 내 의료종사자 및 임상병리사들의 병원 감염을 예방하고자 생물학적 안전에 관한 가이드라인을 확인하였다. 국내 임상병리사들의 경험과 그로부터 얻은 교훈을 통해 국내외 COVID-19 팬데믹 상황으로부터 국민의 안전을 지킬 수 있는 단초를 제공할 수 있을 것이라 사료된다.
In December 2019, the first coronavirus disease- 2019 (COVID-19) patient was reported in Wuhan, Hubei Province, China. Since then, the number of patients who suffered severe acute respiratory syndrome caused by the novel Coronavirus (SARS-CoV-2 or 2019-nCoV) has increased dramatically in Korea. This new variant virus induces pulmonary diseases, including cough, sore throat, rhinorrhea, dyspnea, and pneumonia. Because SARS-CoV-2 is an RNA virus, real-time reversetranscriptase PCR has been used widely to diagnose COVID-19. As the Korea Centers for Disease Prevention and Control (KCDC) and Ministry of Food & Drug Safety (MFDS) approved emergency use authorization, clinical specimens collected from COVID-19 patients and even healthy people have been clinically diagnosed by laboratory medicine. Based on a literature search, this paper reviews the epidemiology, symptoms, molecular diagnostics approved by KCDC, a current diagnosis of COVID-19 in the laboratories, the difference between molecular and serological diagnosis, and guidelines for clinical specimens. In addition, the Korean guidelines of biosafety for clinical laboratory scientists are evaluated to prevent healthcare-associated infection. The author’s experience and lessons as clinical laboratory scientists will provide valuable insights to protect the domestic and international health community in this COVID-19 pandemic around the world.
Although various endoscopic techniques in situs inversus have been reported, endoscopic retrograde cholangiopancreatography (ERCP) in patients with situs inversus is always challenging even for an ...experienced endoscopist. We performed ERCP using two different techniques, and compare the merits of each technique.
A 74-year-old woman presented with epigastric pain and jaundice for 3 days. Computed tomography revealed diffuse dilatation of the biliary tree, with multiple intrahepatic duct and common bile duct (CBD) stones, in addition to situs inversus totalis. ERCP was performed twice for CBD stone to remove the CBD stones using two techniques. For the first technique used, the patient was placed in a prone position with the endoscopist on the right side of the table. First, the endoscope was rotated 180° counterclockwise in the stomach, and was then shortened by turning 180° the counterclockwise again in the duodenum. For the second technique, we assessed the second portion of the duodenum by following the lesser curvature, while slowly turning the endoscope clockwise.
We present an unusual case of biliary stones in a patient with situs inversus who was treated using modified ERCP techniques.
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