A Case of Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. It occurs in patients with structurally normal heart and causes exercise-emotion-triggered syncope and sudden cardiac death. We experienced a case of CPVT in an 11 year-old female patient who was admitted for sudden cardiovascular collapse. The initial electrocardiogram (ECG) on emergency department revealed ventricular fibrillation. After multiple defibrillations, sinus rhythm was restored. However, recurrent ventricular fibrillation occurred during insertion of nasogastric tube without sedation in coronary care unit. On ECG monitoring, bidirectional ventricular tachycardia occurred with sinus tachycardia and then degenerated into ventricular fibrillation. To our knowledge, there has been no previous case report of CPVT triggered by sinus tachycardia in Korea. Therefore, we report the case as well as a review of the literature

Histopathological retrospective study of canine renal disease in Korea, 2003~2008

Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson's trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations

Pro- and anti-inflammatory cytokine expression and histopathological characteristics in canine brain with traumatic brain injury

We analyzed the expression level and cellular localization of pro- and anti-inflammatory cytokines and histopathologically characterized canine traumatic brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and vasogenic edema. Immunohistochemical evaluations suggested that both pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta (TGF-β)] were highly expressed in neurons and neutrophils. In particular, the highest magnitude of expression was identified for IL-1β and TGF-β. This data helps describe the pathologic characteristics of canine TBI, and may help in the design of potential therapeutic approaches to control secondary damage by inflammatory cytokines

Integrated Expression Profiling and Genome-Wide Analysis of ChREBP Targets Reveals the Dual Role for ChREBP in Glucose-Regulated Gene Expression

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator

Prevalence and detection of low-allele-fraction variants in clinical cancer samples

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay

GPR55 Antagonist CID16020046 Protects against Atherosclerosis Development in Mice by Inhibiting Monocyte Adhesion and Mac-1 Expression

GPR55 recognizes several lipid molecules such as lysophosphatidylinositol. GPR55 expression was reported in human monocytes. However, its role in monocyte adhesion and atherosclerosis development has not been studied. The role of GPR55 in monocyte adhesion and atherosclerosis development was investigated in human THP-1 monocytes and ApoE−/− mice using O-1602 (a potent agonist of GPR55) and CID16020046 (a specific GPR55 antagonist). O-1602 treatment significantly increased monocyte adhesion to human umbilical vein endothelial cells, and the O-1602-induced adhesion was inhibited by treatment with CID16020046. O-1602 induced the expression of Mac-1 adhesion molecules, whereas CID16020046 inhibited this induction. Analysis of the promoter region of Mac-1 elucidated the binding sites of AP-1 and NF-κB between nucleotides −750 and −503 as GPR55 responsive elements. O-1602 induction of Mac-1 was found to be dependent on the signaling components of GPR55, that is, Gq protein, Ca2+, CaMKK, and PI3K. In Apo−/− mice, administration of CID16020046 ameliorated high-fat diet-induced atherosclerosis development. These results suggest that high-fat diet-induced GPR55 activation leads to the adhesion of monocytes to endothelial cells via induction of Mac-1, and CID16020046 blockage of GPR55 could suppress monocyte adhesion to vascular endothelial cells through suppression of Mac-1 expression, leading to protection against the development of atherosclerosis

AR6 SSP-RCP 시나리오 기반 동아시아 열스트레스 발생특성의 미래전망

기후변화 영향평가 및 대응대책의 지원을 위해서는 다양한 부문에 대한 상세 기후변화 영향정보의 분석 및 평가가 필요하다. 최근 여름철 폭염의 빈번한 출현과 강도의 강화로 열 관련 질병과 사망률 이 높아짐에 따라, 열스트레스와 같이 보건부문에서 활용 가능한 응용정보의 필요성이 증가하고 있다. 본 연구에서는 열스트레스의 대표지수인 WBGT(wet bulb globe temperature)를 이용하여 미래의 동아시아 열스트레스 발생특성을 전망하였다. 이를 위해 편의보정된 CORDEX 동아시아 지역기후모델(HadGEM-RA, CCLM, WRF, RegCM, GRIMs) 모의자료를 4종의 SSP(SSP1-2.6, 2-4.5, 3-7.0, 5-8.5) 시나리오에 대하여 분석하였다. 21세기 후반기(2081-2100년)의 동아시아 여름철 평균 열스트레스는 현재(1979-2014년) 대비 +3.1 (SSP1-2.6)에서 +7.5 (SSP5-8.5)까지 상승하였다. 기온과 상대습도의 함수로 산출되는 열스트레스의 변화는 대부분이 기온에 의해 설명되지만, 지역과 시나리오에 따라 상대습도의 변화가 열스트레스를 강화 또는 완화시키는 것으로 나타났다. 21세기 후반기에 중국 북부에서는 여름철 평균 상대습도가 증가하면서 열스트레스가 강화되고, 양쯔강유역과 일본에서는 상대습도가 감소하면서 열스트레스의 증가가 완화될 것으로 전망되었다. 여름철 극한 열스트레스(매년 상위 5%) 발생 시에는 평균상태 보다 상대습도의 기여도가 더 크게 증가하였으며, 고배출 시나리오에 비해 저배출 시나리오에서 그 영향이 더 뚜렷하였다. 동아시아를 6개 세부영역(중국 북부, 북동부, 남부, 양쯔강유역, 한반도, 일본)으로 구분하여 영역별 극한 열스트레스일을 분석한 결과, 고배출 시나리오에서 모든 영역의 극한 열스트레스일은 21세기 후반기에 현재보다 10배 빈번하게 발생하며, 강도가 강해지고 발생면적 또한 넓어져 열스트레스의 영향이 크게 증가할 것으로 전망되었다. 극한 열스트레스일의 발생 시작일은 앞당겨지고, 종료일은 늦어질 것으로 전망되며, 고배출 시나리오일수록 발생기간이 크게 확장될 것으로 전망되었다. 현재 각 세부영역에서 평균 5 6일 정도 지속되어 발생하는 극한 열스트레스일이 고배출 시나리오에서는 21세기 후반기에 평균 80일 이상 지속되어 여름철 대부분의 기간에 극한현상이 지속적으로 발생할 것으로 전망되었다.2