N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity is one of the major causes for neuronal cell death during cerebral ischemic insult. Previously, we reported that the final product of lipid membrane peroxidation 4-hydroxy-2E-nonenal (HNE) synergistically increased NMDA receptor-mediated excitotoxicity (J Neurochem., 2006). In this study, we investigated the mechanism involved in the synergistic neuronal cell death induced by co-treatment with HNE and NMDA. Although neither HNE (1 microM) nor NMDA (2 microM) alone induced the death of cortical neurons, simultaneous treatment of neuronal cells with HNE and NMDA synergistically evoked the death of the cells. However, the synergistic effect on neuronal death was observed only in the presence of calcium. HNE neither increased the cytosolic calcium level ([Ca2+]i) nor altered the NMDA-induced intracellular calcium influx. However, HNE together with NMDA elevated the mitochondrial calcium level and depolarized the mitochondrial transmembrane potential. Furthermore, HNE evoked damage of isolated mitochondria at the cytosolic calcium level (200 nM), which is maximally induced by 2 microM NMDA. Consistently, ATP was depleted in neurons when treated with both HNE and NMDA together. Ciclopirox, a potent inhibitor of mitochondrial permeability transition pore opening (Br. J. Pharmacol., 2005), largely prevented the synergistic damage of mitochondria and death of cortical neurons. Therefore, although low concentrations of HNE and NMDA cannot individually induce neuronal cell death, they can evoke the neuronal cell death by synergistically accelerating mitochondrial dysfunction.
Adenosine Triphosphate ; Calcium ; Cell Death ; Cytosol ; Membrane Potentials ; Membranes ; Mitochondria ; Mitochondrial Membrane Transport Proteins ; N-Methylaspartate ; Neurons ; Permeability ; Pyridones

Since the existence of cell-free fetal DNA (cff-DNA) in maternal circulation was discovered, it has been identified as a promising source of fetal genetic material in the development of reliable methods for non-invasive prenatal diagnosis (NIPD) of fetal trisomy 21 (T21). Currently, a prenatal diagnosis of fetal T21 is achieved through invasive techniques, such as chorionic villus sampling or amniocentesis. However, such invasive diagnostic tests are expensive, require expert technicians, and have a miscarriage risk approximately 1%. Therefore, NIPD using cff-DNA in the detection of fetal T21 is significant in prenatal care. Recently, the application of new techniques using single-molecular counting methods and the development of fetal-specific epigenetic markers has opened up new possibilities in the NIPD of fetal T21 using cff-DNA. These new technologies will facilitate safer, more sensitive and accurate prenatal tests in the near future. In this review, we investigate the recent methods for the NIPD of fetal T21 and discuss their implications in future clinical practice.
Abortion, Spontaneous ; Amniocentesis ; Chorionic Villi Sampling ; Diagnostic Tests, Routine ; DNA ; Down Syndrome ; Epigenomics ; Female ; Humans ; Pregnancy ; Prenatal Care ; Prenatal Diagnosis ; Trisomy

PURPOSE: Preeclampsia is a major cause of maternal and perinatal mortality and morbidity and is considered to be a multifactorial disorder involving a genetic predisposition and environmental factors. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and alterations in the ET-1 system are thought to play a role in triggering the vasoconstriction seen with preeclampsia. The aim of this study was to examine the frequency of the 4 common single-nucleotide polymorphisms (SNPs) (c.1370T>G, c.137_139delinsA, c.3539+2T>C, and c.5665G>T) of the ET-1 gene in normotensive and preeclamptic pregnancies and to investigate whether these SNPs are associated with preeclampsia in pregnant Korean women. METHODS: We analyzed blood samples from 206 preeclamptic and 216 normotensive pregnancies using a commercially available SNapShot kit and an ABI Prism 3100 Genetic analyzer. RESULTS: There were no significant differences in genotype or allele frequencies of the 4 SNPs in the ET-1 gene between preeclamptic and normotensive pregnancies. The respective frequencies of the 3 haplotypes (TDTG, GDCT, and TICT; >10% haplotype frequency) were 61%, 13% and 13%, respectively, in preeclampsic pregnancies and 62%, 14% and 12%, respectively, in normotensive pregnancies. The frequencies of these haplotypes were similar for both groups. Using multiple logistic regression analysis, we did not observe an increase in the risk of preeclampsia for the 4 SNPs of the ET-1 gene under either a recessive or dominant model. CONCLUSION: This study suggests that the 4 SNPs of the ET-1 gene are not associated with an increased risk for preeclampsia in pregnant Korean women.
Endothelin-1 ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Logistic Models ; Perinatal Mortality ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; Pregnancy ; Vasoconstriction

PURPOSE: Preeclampsia is a multifactorial disorder with genetic and environmental components. Recently, the STOX1 gene, identified as a candidate gene for preeclampsia in Dutch women, has been shown to be placentally expressed and subject to imprinting with preferential transmission of the maternal allele. The purpose of this study is to investigate whether there is an association between the STOX1 Y153H variation and preeclampsia in Korean pregnant women. MATERIALS AND METHODS: This study involved 202 preeclamptic and 204 healthy pregnant women who were genotyped for the Y153H variant of the STOX1 gene using a commercially available SNapShot assay kit and an ABI Prism 3730 DNA Analyzer. RESULTS: There were no significant differences in genotype frequencies of the Y153H variant of the STOX1 gene between preeclamptic patients and normal controls (P>0.05). The H allele frequency of the STOX1 Y153H variation was similar in patients with preeclampsia (87.1%) and in normal controls (86.5%). In addition, multiple logistic regression analysis showed that the YH, HH, and YH/HH genotypes were not associated with an increased risk of preeclampsia when compared to the YY genotype. CONCLUSION: This is the first study to characterize the Y153H variant of the STOX1 gene in Korean patients with preeclampsia. We found no differences in the genotype and allele frequencies between preeclamptic and normal pregnancies. Although limited by a relatively small sample size, our study suggests that the STOX1 Y153H variation is not associated with the development of preeclampsia in Korean pregnant women.
Alleles ; DNA ; Female ; Gene Frequency ; Genotype ; Humans ; Logistic Models ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Sample Size

PURPOSE: To compare the accuracy of thick-and thin-section spiral CT and to determine whether, in diagnosing mediastinal lymph node metastasis from non-small cell lung cancer, the latter is superior to the former. MATERIALS AND METHODS: Between March 1997 and March 1998, 51 patients with pathologically proven non-s-mall cell lung cancer underwent thoracotomy with full nodal dissection. Thick- and thin-section spiral CT were performed in all patients, with a mean interval of 14 days. The former was performed with 10 mm thick-ness and 10 mm interval, and the latter with 3 mm thickness and 3 mm interval. Mediastinal lymph nodes were localized according to the lymph node mapping scheme of the American Thoracic Society and were considered positive for metastasis if they exceeded 10 mm in short-axis diameter. RESULTS: A total of 227 mediastinal nodal stations in 51 patients were obtained. Of these, 188 stations included in thin-section spiral CT were analyzed and the prevalence of ediastinal nodal metastasis was found to be 10%. On a station-by-station basis, and for thick-and thin-section spiral CT, respectively, the overall sensitivi-ties of mediastinal lymph node metastasis were 32% and 53% (p < .05), while specificities were 91% and 92% (p> .05). Although there were no statistically significant differences in sensitivity and specificity according to nodal station, thin-section spiral CT tended to be superior to the thick-section type for stations 7 and 10R in terms of sensitivity, and for stations 4L and 5 in terms of specificity. CONCLUSION: Thin-section spiral CT was more sensitive than thick-section spiral CT is the evaluation of medi-astinal lymph node metastasis from non-small cell lung cancer. This may be due to the higher resolution of the former and its ability to discriminate between lymph node and vessel.
Carcinoma, Non-Small-Cell Lung* ; Humans ; Lung Neoplasms ; Lymph Nodes* ; Neoplasm Metastasis* ; Prevalence ; Sensitivity and Specificity ; Thoracotomy ; Tomography, Spiral Computed*

Cell-free fetal nucleic acids in the maternal circulation can be broadly divided into fetal DNA and RNA that originate from apoptotic placenta cells. Cell-free fetal nucleic acids can be detected from 4-5 weeks gestation and are undetectable in the maternal circulation after delivery. Therefore, cell-free fetal nucleic acids have been proposed as a potential material for non-invasive prenatal diagnosis (NIPD), which poses no risk to mother and child. The clinical applications of this technology fall into three categories: first, early sex determination in cases at high risk of X-linked disorders or congenital adrenal hyperplasia requiring follow-up testing or antenatal treatment; second, detection of specific paternally inherited monogenic diseases in families with high genetic risk; and third, routine antenatal care offered to all pregnant women, including prenatal screening/diagnosis of aneuploidy, particularly Down syndrome. Fetal sex determination is already performed in routine clinical care for high-risk individuals in some countries. Many researchers have explored the possibility of cell-free fetal nucleic acids on NIPD of monogenic diseases and aneuploidy. Promising results have been reported from studies using the combination of markers and the application of various experimental methods. Although these technologies can raise ethical, social, and legal concerns, a reliable noninvasive test using cell-free fetal nucleic acids may in future form a part of national antenatal programs for detection of Down syndrome and other common genetic disorders.
Adrenal Hyperplasia, Congenital ; Aneuploidy ; Child ; DNA ; Down Syndrome ; Female ; Follow-Up Studies ; Humans ; Mothers ; Nucleic Acids ; Placenta ; Pregnancy ; Pregnant Women ; Prenatal Diagnosis ; RNA

OBJECTIVE: The purposes of this study were to evaluate size-specific dose estimate (SSDE) of low-dose CT (LDCT) in the Korean Lung Cancer Screening (K-LUCAS) project and to determine whether CT protocols from Western countries are appropriate for lung cancer screening in Korea. MATERIALS AND METHODS: For participants (n = 256, four institutions) of K-LUCAS pilot study, volume CT dose index (CTDI(vol)) using a 32-cm diameter reference phantom was compared with SSDE, which was recalculated from CTDI(vol) using size-dependent conversion factor (f-size) based on the body size, as described in the American Association of Physicists in Medicine Report 204. This comparison was subsequently assessed by body mass index (BMI) levels (underweight/normal vs. overweight/obese), and automatic exposure control (AEC) adaptation (yes/no). RESULTS: Size-specific dose estimate was higher than CTDI(vol) (2.22 ± 0.75 mGy vs. 1.67 ± 0.60 mGy, p < 0.001), since the f-size was larger than 1.0 for all participants. The ratio of SSDE to CTDI(vol) was higher in lower BMI groups; 1.26, 1.37, 1.43, and 1.53 in the obese (n = 103), overweight (n = 70), normal (n = 75), and underweight (n = 4), respectively. The ratio of SSDE to CTDI(vol) was greater in standard-sized participants than in large-sized participants independent of AEC adaptation; with AEC, SSDE/CTDI(vol) in large- vs. standard-sized participants: 1.30 ± 0.08 vs. 1.44 ± 0.08 (p < 0.001) and without AEC, 1.32 ± 0.08 vs. 1.42 ± 0.06 (p < 0.001). CONCLUSION: Volume CT dose index based on a reference phantom underestimates radiation exposure of LDCT in standard-sized Korean participants. The optimal radiation dose limit needs to be verified for standard-sized Korean participants.
Body Mass Index ; Body Size ; Cone-Beam Computed Tomography ; Humans ; Korea ; Lung Neoplasms* ; Lung* ; Mass Screening* ; Overweight ; Pilot Projects ; Radiation Dosage ; Radiation Exposure ; Thinness ; Tomography, X-Ray Computed

OBJECTIVE: To report the radiological results of a pilot study for the Korean Lung Cancer Screening project conducted to evaluate the feasibility of lung cancer screening using low-dose chest computed tomography (LDCT) in Korea. MATERIALS AND METHODS: The National Cancer Center and three regional cancer centers participated in this study. Asymptomatic current or ex-smokers aged 55–74 years with a smoking history of at least 30 pack-years who had used tobacco within the last 15 years were considered eligible. In total, 256 participants underwent LDCT November 2016 through March 2017. The American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) was used to categorize the LDCT findings. RESULTS: In total, 57%, 35.5%, 3.9%, and 3.5% participants belonged to Lung-RADS categories 1, 2, 3, and 4, respectively. Accordingly, 7.4% participants exhibited positive findings (category 3 or 4). Lung cancer was diagnosed in one participant (stage IA, small cell lung cancer). Other LDCT findings included pulmonary emphysema (32.8%), coronary artery calcification (30.9%), old pulmonary tuberculosis (11.7%), bronchiectasis (12.9%), interstitial lung disease with a usual interstitial pneumonia pattern (1.2%), and pleural effusion (0.8%). CONCLUSION: Even though the size of our study population was small, the positive rate of 7.4% was like or lower than those in other lung cancer screening studies. Early lung cancer was detected using LDCT screening in one participant. Lung-RADS may be applicable to participants in Korea, where pulmonary tuberculosis is endemic.
Bronchiectasis ; Coronary Vessels ; Idiopathic Pulmonary Fibrosis ; Information Systems* ; Korea ; Lung Diseases, Interstitial ; Lung Neoplasms* ; Lung* ; Mass Screening* ; Pilot Projects* ; Pleural Effusion ; Pulmonary Emphysema ; Smoke ; Smoking ; Thorax ; Tobacco ; Tuberculosis, Pulmonary

Background: Pyruvate dehydrogenase complex (PDHC) deficiency is a rare mitochondrial disorder caused by a genetic mutation affecting the activity of the PDHC enzyme, which plays a major role in the tricarboxylic cycle. Few cases of surgery or anesthesia have been reported. Moreover, there is no recommended anesthetic method.Case: A 24-month-old child with a PDHC deficiency presented to the emergency room with respiratory failure, mental decline, systemic cyanosis, and lactic acidosis. During hospitalization period, the patient presented with pneumothorax, pneumoperitoneum, and multiple air pockets in the heart. Two surgeries were performed under general anesthesia using an inhalational anesthetic agent. The patient was discharged with home ventilation. Conclusions Anesthesiologists should be wary of multiple factors when administering anesthesia to patients with PDHC deficiency, including airway abnormalities, acid-base imbalance, intraoperative fluid management, selection of appropriate anesthetics, and monitoring of lactic acid levels.

PURPOSE: To find the most effective method for extraction of cell-free DNA (cf-DNA) from maternal plasma, we compared a blood DNA extraction system (blood kit) and a viral DNA extraction system (viral kit) for non-invasive first-trimester fetal gender determination. MATERIALS AND METHODS: A prospective cohort study was conducted with maternal plasma collected from 44 women in the first-trimester of pregnancy. The cf-DNA was extracted from maternal plasma using a blood kit and a viral kit. Quantitative fluorescent-polymerase chain reaction (QF-PCR) was used to detect the SRY gene and AMEL gene. The diagnostic accuracy of the QF-PCR results was determined based on comparison with the final delivery records. RESULTS: A total of 44 women were tested, but the final delivery record was only obtained in 36 cases which included 16 male-bearing and 20 female-bearing pregnancies. For the blood kit and viral kit, the diagnostic accuracies for fetal gender determination were 63.9% (23/36) and 97.2% (35/36), respectively. CONCLUSION: In non-invasive first-trimester fetal gender determination by QF-PCR, using a viral kit for extraction of cf-DNA may result in a higher diagnostic accuracy.
Cohort Studies ; DNA ; DNA, Viral ; Female ; Genes, sry ; Humans ; Plasma ; Pregnancy ; Prospective Studies