Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation

AbstractIntroductionNeutrophils can be induced to release DNA combined with histones. The resulting neutrophil extracellular trap (NET) provides a scaffold for growing hemostatic plug. Therefore, the NET formation may be inevitable in clinical conditions that are characterized by formation of vascular thrombi. Thus far, there have been no reports on the clinical significance of NET in disseminated intravascular coagulation (DIC). Therefore, we investigated circulating levels of NET in DIC and analyzed their potential values to assess coagulation severity and predict clinical outcome.MethodsThe plasma levels of DNA-histone complexes and double-stranded DNA (dsDNA), considered to be in vivo markers of NET, were measured in 199 patients suspected of having DIC and 20 healthy controls.ResultThe circulating levels of DNA-histone complexes and dsDNA were significantly elevated in overt-DIC. The increased levels of these two markers correlated with the severity of coagulopathy including DIC score and D-dimer. Multivariable Cox regression analysis, adjusted for the conventional DIC markers, revealed that elevated DNA-histone complexes and dsDNA are poor independent prognostic markers.ConclusionThe circulating levels of NET release reflect the coagulation activation and adverse clinical outcomes in patients with DIC, thereby providing potential clinical relevance for mortality prediction in DIC

Hydraulic and ecological changes under drainage gate operations with coupled model SCHISM-CoSiNE in Saemangeum basin, Korea

The drainage gates have been controlled for desalination under normal conditions and flood defense in  Saemangeum basin, Korea. Recently, it became an issue that the gates have been opened not to deteriorate water quality in the lake. It is, thus, necessary to precisely estimate the changes of water quality characteristics, especially DO, phosphate and nitrate, in the lake according to various gate operations. In this study, Semi-implicit Cross-scale Hydroscience Integrated System Model and Carbon, Silicate, Nitrogen Ecosystem model (SCHISM-CoSiNE) which is cable to simulate dynamic exchange such as gate operation conditions was utilized to obtain reliable and reasonable results including hydrodyanamic and environmental variables. For the verification, the measured data at 6 locations in Saemangeum basin was used to compare  incluidng temperatue and salintiy from 2016 and each relative error became small enough to show high accurary. Also, under various scenarios by changing the designated water surface elevation on flood seasons, this model has been applied to present the best designated water surface elevation in terms of both water quality and water supply in the Saemangeum basin. It becomes possbile to show reliable guidance for dynamic operations and environmental changes with this model as requested in near future

Selection of Elevation Models for Flood Inundation Map Generation in Small Urban Stream: Case Study of Anyang Stream

To reduce flood damages, the Ministry of Environment in Korea has provided a flood inundation map so that people can expediently identify flood-prone areas. However, the current flood inundation maps have been produced based on the DEM which makes it difficult to represent realistic situations due to the lack of reproduction of land surface conditions. This study aims to provide more accurate and detailed flood inundation maps for flooding events due to river overflow in small urban areas. In this study, flood inundation analysis is performed using the river analysis system, HEC-RAS 2D, with the DSM and the DEM of urban areas in the Anyang Stream Basin, Korea to examine the differences in terms of terrain data and flooded area. Finally, for urban areas with dense buildings and congested road networks, the flood inundation analysis based on DSM can represent a more realistic flood situation and create an appropriate flood inundation map

Hyaluronan- and RNA-binding deubiquitinating enzymes of USP17 family members associated with cell viability

BACKGROUND: Protein degradation by the ubiquitin system plays a crucial role in numerous cellular signaling pathways. Deubiquitination, a reversal of ubiquitination, has been recognized as an important regulatory step in the ubiquitin-dependent degradation pathway. RESULTS: While identifying putative ubiquitin specific protease (USP) enzymes that contain a conserved Asp (I) domain in humans, 4 USP17 subfamily members, highly homologous to DUB-3, have been found (USP17K, USP17L, USP17M, and USP17N), from human chorionic villi. Expression analysis showed that USP17 transcripts are highly expressed in the heart, liver, and pancreas and are expressed moderately in various human cancerous cell lines. Amino acid sequence analysis revealed that they contain the highly conserved Cys, His, and Asp domains which are responsible for the deubiquitinating activity. Biochemical enzyme assays indicated that they have deubiquitinating activity. Interestingly, the sequence analysis showed that these proteins, with exception of USP17N, contain the putative hyaluronan/RNA binding motifs, and cetylpyridinium chloride (CPC)-precipitation analysis confirmed the association between these proteins and intracellular hyaluronan and RNA. CONCLUSION: Here, we report that the overexpression of these proteins, with exception of USP17N, leads to apoptosis, suggesting that the hyaluronan and RNA binding motifs in these enzymes play an important role in regulating signal transduction involved in cell death

Substitution of Heavy Complementarity Determining Region 3 (CDR-H3) Residues Can Synergistically Enhance Functional Activity of Antibody and Its Binding Affinity to HER2 Antigen

To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their anti-proliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity (IC50: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity (K-D : 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCI-N82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.OAIID:RECH_ACHV_DSTSH_NO:T201620640RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A002901CITE_RATE:2.67DEPT_NM:화학생물공학부EMAIL:[email protected]_YN:YCONFIRM:

Electro-Mechanical Safety Testing of Portable ECG Devices for Home Healthcare Usage

OBJECTIVES: This paper suggests the experimental guidelines to evaluate the electro-mechanical safety of belt type equipment. The electro-mechanical safety was determined by using the International Electrotechnical Commission guidelines, which are widely used as important factors for assessing the electro-mechanical safety of belt type equipment. However, the local guidelines on wearable healthcare sensors are currently not well-established. Therefore, safety guidelines suited for the actual circumstances in Korea are required, and this paper attempts to try a new experimental safety test procedure of the wearable healthcare sensor. METHODS: This belt type device measures the electrocardiogram (ECG) and heart rates by attaching to the chest. Examination lists were selected by analyzing the common standards ofelectro-mechanical safety (IEC 60601-1) and environment tests (IEC 60068-1, IEC 60068-2) of home-healthcare equipment. RESULTS: The essential electrical safety, which was required for the RS300G3 as a medical device, was evaluated, and most of the examination lists were selected by considering the circumstances of the users. The device passed all the selected examinable lists that are applicable to the Korean environment. CONCLUSIONS: This study has limitations to estimate and to conduct electro-mechanical safety experiments because our study focused on the belt type of heart-rates equipment. We are not taking into account the overall electro-mechanical home-healthcare measurements. According to industrial and technological development, there are infinite possibilities for the advancement of home-healthcare equipment, so more examination lists for safety are being added in addition to what we have doneope

Association between maternal coronavirus disease 2019 and transient tachypnea of the newborn: a single-center study

Background Limited clinical reports have investigated the effects of maternal coronavirus disease 2019 (COVID-19) on fetuses and neonates. Purpose This retrospective study aimed to assess the impact of maternal COVID-19 on neonates during the perinatal period, including neonatal clinical outcomes, versus the outcomes of neonates of mothers without COVID-19. Methods Neonates born to COVID-19-infected mothers at the National Health Insurance Service Ilsan Hospital between February 2021 and March 2022 were included. Those with gestational age (GA) ≥35+0 weeks who were born within 2 weeks of the maternal infection were matched 1:2 with a control group based on GA. The main outcomes were respiratory diseases, including transient tachypnea of the newborn (TTN), respiratory distress syndrome, meconium aspiration syndrome, the need for respiratory support, and length of hospital stay. Uni- and multivariate logistic regression analyses were performed and adjusted for relevant covariates, including maternal age, obstetric complications (hypertension and gestational diabetes), delivery mode, birth weight, sex, and small-for-gestational-age status. Results The case group comprised 103 neonates (mean GA, 38.5±1.3 weeks; mean birth weight, 3,121±397 g), while the control group included 206 neonates (mean GA, 38.4±1.2 weeks; mean birth weight, 3088±428 g). In the case and control groups, the proportion of cesarean sections was 91% and 40%, respectively, while the proportion of male infants was 56% and 47%, respectively. After adjusting for covariates, the case group had a higher risk of TTN (adjusted odd ratio [AOR], 3.69; 95% confidence interval [CI], 1.69–8.07), noninvasive respiratory ventilator use (AOR, 2.28; 95% CI, 1.05–4.97), and oxygen support (AOR, 4.83; 95% CI, 1.46–15.95). Conclusion Newborns born to COVID-19-infected mothers are at increased risk of TTN and may require respiratory support. Close monitoring of respiratory symptoms is crucial in neonates

Effect of 5-aminolevulinic acid-based photodynamic therapy via reactive oxygen species in human cholangiocarcinoma cells

Cancer cells have been reported to exhibit an enhanced capacity for protoporphyrin IX (PpIX) synthesis facilitated by the administration of 5-aminolevulinic acid (ALA). We investigated the effect of ALA-based photodynamic therapy (PDT) on human cholangiocarcinoma cells (HuCC-T1). Since protoporphyrin IX (PpIX), a metabolite of ALA, can produce reactive oxygen species (ROS) under irradiation and then induce phototoxicity, ALA-based PDT is a promising candidate for the treatment of cholangiocarcinoma. When various concentrations of ALA (0.05–2 mM) were used to treat HuCC-T1 cells for 6 or 24 hours, the intracellular PpIX level increased according to the ALA concentration and treatment time. Furthermore, an increased amount of PpIX in HuCC-T1 cells induced increased production of ROS by irradiation, resulting in increased phototoxicity

Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade

Background : Increased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors. Methods : 19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%). Results : In our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6 +/- 4.2%), AC (n=7, 20.0 +/- 4.9%), LCNEC (n=13, 60.0 +/- 21.1%), and SCC (n= 6, 74.2 +/- 16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6 +/- 21.0%) (p=0.000). Conclusions: The results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.This work was supported by grant no 02-2008-029 from the SNUBH Research Fund and partly supported by the Korean Science & Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center at Seoul National University College of Medicine.Song YS, 2008, LUNG CANCER, V61, P54, DOI 10.1016/j.lungcan.2007.11.012Nguyen XC, 2007, EUR J RADIOL, V62, P214, DOI 10.1016/j.ejrad.2006.12.008Khandani AH, 2007, NUCL MED COMMUN, V28, P173Chung JH, 2004, J NUCL MED, V45, P999TRAVIS WD, 2004, WHO INT HISTOLOGICALKalir T, 2002, CANCER, V94, P1078, DOI 10.1002/cncr.10280Wong CYO, 2001, EUR J NUCL MED, V28, P1702Wang BY, 2000, CANCER, V88, P2774Brown RS, 1999, J NUCL MED, V40, P556Ito T, 1998, MODERN PATHOL, V11, P437Travis WD, 1998, HUM PATHOL, V29, P272Baer SC, 1997, J AM ACAD DERMATOL, V37, P575Younes M, 1997, CANCER, V80, P1046Voldstedlund M, 1997, APMIS, V105, P537Haber RS, 1997, THYROID, V7, P363Younes M, 1997, CANCER EPIDEM BIOMAR, V6, P303Younes M, 1996, CLIN CANCER RES, V2, P1151Younes M, 1996, CANCER RES, V56, P1164Younes M, 1995, ANTICANCER RES, V15, P2895NAGASE Y, 1995, J UROLOGY, V153, P798MELLANEN P, 1994, INT J CANCER, V56, P622BROWN RS, 1993, CANCER, V72, P2979TAKATA K, 1992, CELL TISSUE RES, V267, P407PESSIN JE, 1992, ANNU REV PHYSIOL, V54, P911PARDRIDGE WM, 1990, J BIOL CHEM, V265, P18035ISSELBAC.KJ, 1972, NEW ENGL J MED, V286, P929

Sequences of the Cytochrome C Oxidase Subunit I (COI) Gene are Suitable for Species Identification of Korean Calliphorinae Flies of Forensic Importance (Diptera: Calliphoridae)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75068/1/j.1556-4029.2009.01126.x.pd