Circling mouse (C57BL/6J-cir/cir) deleted the transmembrane inner ear (Tmie) gene is an animal model for human non-syndromic recessive deafness, DFNB6. In circling mouse, hair cells in the cochlea have degenerated and hair bundles have become irregularity as time goes on. Tmie protein carries out a function of the mechanoelectrical transduction channel in cochlear hair cells. Myosin7a (MYO7A) protein has key roles in development of the cochlear hair bundles as well as in the function of cochlear hair cells. To find whether Tmie protein interacts with MYO7A proteins in the cochlea postnatal developmental stage, we investigated expression of the MYO7A proteins in the cochlear hair cells of circling mice by western blot analysis and whole mount immunofluorescence at postnatal day 5 (P5). The expression of MYO7A showed statistically significant increase in the cochlea of C57BL/6J-+/cir and C57BL/6J-cir/cir mice than that of C57BL/6J-+/+ mice. The MYO7A intensity of the cochlear hair cells also increased in C57BL/6J-+/cir and C57BL/6J-cir/cir mice compared with those of C57BL/6J-+/+ mice. Taken together, the results indicate that Tmie protein may have an important role with MYO7A protein in the development and maintenance of the stereociliary bundles during postnatal developmental stage of the cochlea.
Animals ; Blotting, Western ; Cochlea ; Deafness ; Ear, Inner ; Fluorescent Antibody Technique ; Hair ; Hair Cells, Auditory* ; Humans ; Mice* ; Models, Animal

Laboratory inbred mice are used widely and commonly in biomedical research, but inbred mice do not have a big enough gene pool for the research. In this study, genetic and morphometric analyses were performed to obtain data on the characteristics of a newly developing inbred strain (KWM/Hym) captured from Chuncheon, Korea. All of five Korean wild male mice have the zinc-finger Y (ZfY) gene. Also, all of 19 Korean wild mice used in this analysis have the AKV-type murine leukemia virus gene, indicating that Korean wild mice might be Mus musculus musculus. To identify the genetic polymorphism in KWM/Hym, SNP analysis was performed. In a comparison with 28 SNP markers, there was a considerable difference between KWM/Hym and several inbred strains. The homogeneity between KWM/Hym and the inbred strains was as follows: C57BL/6J (39.3%), BALB/c AJic (42.9%), and DBA/2J (50%). KWM/Hym is most similar to the PWK/PhJ inbred strain (96.4%) derived from wild mice (Czech Republic). To identify the morphometric characteristics of KWM/Hym, the external morphology was measured. The tail ratio of male and female was 79.60±3.09 and 73.55±6.14%, respectively. KWM/Hym has short and agouti-colored hairs and its belly is white with golden hair. Taking these results together, KWM/Hym, a newly developing inbred mouse originated from wild mouse, might be use as new genetic resources to overcome the limitations of the current laboratory mice.
Animals ; Female ; Gangwon-do* ; Gene Pool ; Hair ; Humans ; Korea* ; Leukemia Virus, Murine ; Male ; Mice* ; Polymorphism, Genetic ; Tail

The fate of a grafted radial artery remains unknown. The purpose of this study was to determine whether the preoperative severity of stenosis of the target vessel influence short-term patency of radial artery (RA) grafts used as coronary artery bypass conduits. In 54 patients who had coronary artery bypass grafting (CABG) with RA grafts, RA patency was determined with multi-slice computed tomography (MSCT) 1 year after CABG. These patients were divided into three groups on the basis of the percentage of the target vessel stenosis: mild (< 60%, n=17), moderate (60% to 79%, n=19), and severe (> or = 80%, n=18). MSCT was also performed 1 week later to exclude early occlusion of RA grafts. In 3 patients, the MSCT failed to adequately discriminate the status of the RA graft due to poor image resolution. The overall incidence of RA occlusion was 23.5% (12 of 51) at 1 year in the entire population. The mild stenosis, moderate stenosis and severe stenosis group showed an occlusion rate of 50% (8 of 16), 23.5% (4 of 17) and 0% (0 of 18), respectively. The severe stenosis group had significantly lower rate of RA graft occlusion compared to the mild stenosis group (p< 0.001) and moderate stenosis group (p< 0.05). No difference in occlusion between grafts used for the different coronary artery branches could be demonstrated. Preoperative severity of the target coronary artery significantly affected the short-term RA grafts patency. Correct indication is the key factor for short-term RA patency.
Aged ; Coronary Arteriosclerosis/pathology/*radiography/*surgery ; Coronary Artery Bypass/*methods ; Coronary Vessels/pathology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Postoperative Complications/epidemiology ; Radial Artery/*transplantation ; Severity of Illness Index ; Tomography, X-Ray Computed ; Vascular Patency

PURPOSE: The arrhythmogenic effect of stem cells transplantation (SCT) in an infarct myocardium is still unknown. We investigated arrhythmogenicity of SCT in rat cryo-infarct model. MATERIALS AND METHODS: In rat cryo-infarct model, bone marrow mononuclear stem cells (MNSC, 1 x 10(7) cells) were transplanted into the infarct border zone (BZ) of the LV epicardium. We compared the optical mapping and inducibility of ventricular tachycardia/fibrillation (VT/VF) among normal (n=5), cryo-infarct (n=6), and SCT rats (n=6). RESULTS: The VT/VF inducibility was higher in the cryo- infarct (47.2%, p=0.001) and SCT groups (34.6%, p=0.01) than in the normal group (12.8%). The induced VT/VF episodes persisted for more than 2 minutes in 4.3%, 26.4% and 17.3% in the normal, cryo-infarct and SCT group, respectively. In the SCT group, the action potential duration at 70% was shorter at the SCT site than the BZ during SR (75.2 +/- 8.1 vs. 145.6 +/- 4.4 ms, p=0.001) and VT (78.2 +/- 13.0 vs. 125.7 +/- 21.0 ms, p= 0.001). Conduction block was observed at the SCT site and BZ during VT. However, no reentry or ectopic foci were observed around the SCT sites. CONCLUSION: The electrical conduction was improved by SCT without evidence of augmentation of arrhythmia in the rat cryo-infarct model.
Action Potentials ; Animals ; Arrhythmias, Cardiac/*etiology ; Bone Marrow Transplantation/*adverse effects ; Disease Models, Animal ; Electric Conductivity ; Heart Ventricles/pathology/transplantation ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Myocardial Infarction/pathology/*surgery ; Rats ; Rats, Sprague-Dawley

OBJECTIVES: The purpose of this study was to examine the associations of childbirth, breastfeeding, and their interaction with breast cancer (BC) risk reduction, and to evaluate the heterogeneity in the BC risk reduction effects of these factors by menopause, hormone receptor (HR) status, and pathological subtype. METHODS: BC patients aged 40+ from the Korean Breast Cancer Registry in 2004-2012 and controls from the Health Examinee cohort participants were included in this study after 1:1 matching (12 889 pairs) by age and enrollment year. BC risk according to childbirth, breastfeeding, and their interaction was calculated in logistic regression models using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: BC risk decreased with childbirth (3+ childbirths relative to 1 childbirth: OR, 0.66; 95% CI, 0.56 to 0.78 and OR, 0.80; 95% CI, 0.68 to 0.95 in postmenopausal and premenopausal women, respectively); and the degree of risk reduction by the number of children was heterogeneous according to menopausal status (p-heterogeneity=0.04), HR status (p-heterogeneity < 0.001), and pathological subtype (p-heterogeneity < 0.001); whereas breastfeeding for 1-12 months showed a heterogeneous association with BC risk according to menopausal status, with risk reduction only in premenopausal women (p-heterogeneity < 0.05). The combination of 2 more childbirths and breastfeeding for ≥13 months had a much stronger BC risk reduction of 49% (OR, 0.51; 95% CI, 0.45 to 0.58). CONCLUSIONS: This study suggests that the combination of longer breastfeeding and more childbirths reduces BC risk more strongly, and that women who experience both 2 or more childbirths and breastfeed for ≥13 months can reduce their BC risk by about 50%.
Breast Feeding* ; Breast Neoplasms* ; Breast* ; Child ; Cohort Studies ; Female ; Humans ; Logistic Models ; Menopause ; Odds Ratio ; Parturition* ; Population Characteristics ; Risk Reduction Behavior*

PURPOSE: To overcome the limitations of cancer gene therapy using replication-incom- petent adenovirus, we generated E1B 55 kD-deleted adenovirus (YKL-1) by polymerase chain reaction (PCR) and homologous recombination. We then investigated tumor-specific virus replication and cytotoxicity of YKL-1 in vitro and in vivo. MATERIALS AND METHODS: YKL-1 was constructed by reintroducting E1A and E1B 19 kD into pTG-CMV El/E3-deficient adenoviral vector and inducing homologous recombination in E. coli. The recombinant vector pYKL-1 was transfected into 293 cells to generate YKL-1. The properties of newly constructed YKL-1 was defined by PCR and immuno- blotting analysis. Virus replication was examined by infecting human normal and cancer cells on 6-wells at multiplicity of infection (MOI) of 10 for 3 days. Virus was then recovered and titered. Cytopathic effect was analyzed by infecting human normal and cancer cells on 24-wells at MOIs of 10, 1 or 0.1 for 7 to 10 days and staining them with crystal violet solution. Inhibition of tumor growth was examined in human cancer cell xenografts in nu/nu mice by intratumoral injection of YKL-l. RESULTS: PCR and immunoblotting analysis confirmed that YKL-1 contained E1A and E1B 19 kD but not E1B 55 kD. In human normal cells, virus replication and subsequent cytopathic effect of E1B 55 kD-deleted adenovirus YKL-1 was markedly attenuated by larger than 2 to 3 log in magnitude, compared to that of wild-type ad-XJ. In contrast, YKL-1 was capable of replicating and inducing cytotoxicity i.n most human cancer cells. C33A and Hep3B containing p53 mutation were much more sensitive, whereas HeLa and H460 with wild type p53 were relatively resistant to YKL-1. Finally, the tumor growth was dramatically retarded by intratumoral injection of YKL-1 in C33A cervical cancer xenograft and the histology showed significant necrosis by intratumoral injection of YKL-1. CONCLUSION: The results here demonstrated the ability of preferential virus replication and cytotoxicity of ElB 55 kD-deleted adenovirus YKL-1 in human cancer cells. Therefore, these indicated a promising potential of YKL-1 as an antitumoral virus agent and a selective replication-competent virus vector.
Adenoviridae* ; Animals ; Genes, Neoplasm ; Genetic Therapy ; Gentian Violet ; Heterografts ; Homologous Recombination ; Humans ; Immunoblotting ; Mice ; Necrosis ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms ; Virus Replication*

Breast cancer is the second leading cancer for Korean women and its incidence rate has been increasing annually. If early diagnosis were implemented with epidemiologic data, the women could easily assess breast cancer risk using internet. National Cancer Institute in the United States has released a Web-based Breast Cancer Risk Assessment Tool based on Gail model. However, it is inapplicable directly to Korean women since breast cancer risk is dependent on race. Also, it shows low accuracy (58%-59%). In this study, breast cancer discrimination models for Korean women are developed using only epidemiological case-control data (n = 4,574). The models are configured by different classification techniques: support vector machine, artificial neural network, and Bayesian network. A 1,000-time repeated random sub-sampling validation is performed for diverse parameter conditions, respectively. The performance is evaluated and compared as an area under the receiver operating characteristic curve (AUC). According to age group and classification techniques, AUC, accuracy, sensitivity, specificity, and calculation time of all models were calculated and compared. Although the support vector machine took the longest calculation time, the highest classification performance has been achieved in the case of women older than 50 yr (AUC = 64%). The proposed model is dependent on demographic characteristics, reproductive factors, and lifestyle habits without using any clinical or genetic test. It is expected that the model could be implemented as a web-based discrimination tool for breast cancer. This tool can encourage potential breast cancer prone women to go the hospital for diagnostic tests.
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/*epidemiology ; Diagnosis, Computer-Assisted/*methods ; Early Detection of Cancer/*methods ; Female ; Humans ; *Machine Learning ; Middle Aged ; Pattern Recognition, Automated/methods ; Prevalence ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Assessment/methods ; Risk Factors ; Sensitivity and Specificity ; Women's Health/*statistics & numerical data

BACKGROUND/AIMS: The optimal strategy for anticoagulation treatment in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has not been established. We evaluated the efficacy and bleeding risk of warfarin and antiplatelet agents in patients with AF and ESRD. METHODS: We retrospectively reviewed the medical records of 256 patients with AF and ESRD and included 158 patients (age, 63.7 ± 12.2 years; male sex, n = 103) with a CHA2DS2-VASc score ≥ 1 who were taking warfarin (n = 53) or an antiplatelet agent (n = 105). RESULTS: During the follow-up period (31.0 ± 29.4 months), 10 ischemic events and 29 major bleeding events occurred. The thromboembolic event rate did not significantly differ between the warfarin and antiplatelet groups (1.9% and 8.6%, respectively; p = 0.166). However, the rate of major bleeding events was significantly higher in the warfarin group than it was in the antiplatelet group (32.1% and 11.4%, respectively; p = 0.002). Cox's regression analysis indicated that warfarin was related to an increased risk of major bleeding events (hazard ratio [HR], 3.44; 95% confidence interval [CI], 1.60–7.36; p = 0.001). Conversely, warfarin was not related to a decreased risk of thromboembolic events (HR, 0.34; 95% CI, 0.04–2.70; p = 0.306). CONCLUSIONS: In patients with AF and ESRD, warfarin use was associated with an increased risk of bleeding events, compared with antiplatelet agents.
Anticoagulants ; Atrial Fibrillation ; Follow-Up Studies ; Hemorrhage ; Humans ; Kidney Failure, Chronic ; Male ; Medical Records ; Platelet Aggregation Inhibitors ; Retrospective Studies ; Warfarin

Background: and Purpose There is no specific indicator for monitoring dementia management. We propose an auxiliary indicator called the community management rate, defined as the proportion of dementia patients who receive informal care from close caregivers or themselves within their community population. The 5-year community management rate is the percentage of dementia patients who are receiving community management at 5 years after they were diagnosed. The aim of this study was to identify how the community management rate has changed over time and how the 5-year community management rate differs according to age, sex, income, residence area, and comorbidities. Methods: We analyzed customized research database of the Korean National Health Insurance Services from 2003 to 2018. The 5-year community management rate was calculated annually with newly diagnosed dementia patients, and compared among subgroups according to age, sex, income, residence area, and comorbidities. Results: This study analyzed 549,297 patients. Among those newly diagnosed with dementia in 2003, the mean duration of community management during the 15-year follow-up was 5.98 years. The community management rate decreased rapidly from 2003 to 2006, after which it increased. A low 5-year community management rate was associated with older age, higher comorbidity burden, nonmetropolitan residence, and low income. Conclusions The community management rate seems to reflect diverse patient factors. Efforts are needed to reduce the comorbidity burden and differences in the 5-year community management rate according to residence area and income. This study indicates the need for further investigations into the use of this indicator to monitor the management of dementia patients.

Background: Inbred mice have several advantages, including genetic similarity to humans, a well-established gene manipulation system, and strong tolerance to inbreeding. However, inbred mice derived from a limited genetic pool have a small genetic diversity. Thus, the development of new inbred strains from wild mice is needed to overcome this limitation. Hence, in this study, we used a new strain of inbred mice called KWM/Hym. We sequenced the Mx1 gene to elucidate the genetic diversities of KWM/Hym mice and observed the biological alterations of the Mx1 protein upon influenza A infection. Results: The Mx1 gene in KWM/Hym mice had 2, 4, and 38 nucleotide substitutions compared to those in the Mx1 gene in A2G, CAST/EiJ, and Mus spretus mice, respectively. Moreover, the Mx1 protein in KWM/Hym mice had 2 and 25 amino acid substitutions compared to those in the Mx1 protein in CAST/EiJ and M. spretus mice, respectively. To elucidate the function of the Mx1 protein, we inoculated the influenza A virus (A/WSN/1933) in KWM/Hym mice. Nine days after infection, all infected KWM/Hym mice survived without any weight loss. Four days after infection, the lungs of the infected KWM/Hym mice showed mild alveolitis and loss of bronchiolar epithelium; however, the pulmonary viral titers of the infected KWM/Hym mice were significantly lower than that in the infected BALB/c mice (2.17 × plaqueforming units mL −1 ). Conclusions Our results demonstrate that the KWM/Hym mice are resistant to influenza A virus infection. Further, these mice can be used as a model organism to understand the mechanism of influenza A virus susceptibility.