• Title/Summary/Keyword: Associated disease

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CRISPR/Cas9-mediated knockout of Rag-2 causes systemic lymphopenia with hypoplastic lymphoid organs in FVB mice

  • Kim, Joo-Il;Park, Jin-Sung;Kim, Hanna;Ryu, Soo-Kyung;Kwak, Jina;Kwon, Euna;Yun, Jun-Won;Nam, Ki-Taek;Lee, Han-Woong;Kang, Byeong-Cheol
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.166-175
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    • 2018
  • Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. Rag-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of Rag-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of Rag-2, we recently established a new Rag-2 knockout FVB mouse line ($Rag-2^{-/-}$) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. $Rag-2^{-/-}$ mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in $Rag-2^{-/-}$ mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in $Rag-2^{-/-}$ mice. These findings indicate that our $Rag-2^{-/-}$ mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

CRISPR/Cas9-mediated knockout of CD47 causes hemolytic anemia with splenomegaly in C57BL/6 mice

  • Kim, Joo-Il;Park, Jin-Sung;Kwak, Jina;Lim, Hyun-Jin;Ryu, Soo-Kyung;Kwon, Euna;Han, Kang-Min;Nam, Ki-Taek;Lee, Han-Woong;Kang, Byeong-Cheol
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.302-310
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    • 2018
  • CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.

Predicting Successful Conservative Surgery after Neoadjuvant Chemotherapy in Hormone Receptor-Positive, HER2-Negative Breast Cancer

  • Ko, Chang Seok;Kim, Kyu Min;Lee, Jong Won;Lee, Han Shin;Lee, Sae Byul;Sohn, Guiyun;Kim, Jisun;Kim, Hee Jeong;Chung, Il Yong;Ko, Beom Seok;Son, Byung Ho;Ahn, Seung Do;Kim, Sung-Bae;Kim, Hak Hee;Ahn, Sei Hyun
    • Journal of Breast Disease
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    • v.6 no.2
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    • pp.52-59
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    • 2018
  • Purpose: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. Methods: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (${\geq}3cm$), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). Results: Small tumor size (p<0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. Conclusion: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.

The correlation between triglyceride to HDL cholesterol ratio and metabolic syndrome, nutrition intake in Korean adults: Korean National Health and Nutrition Examination Survey 2016 (한국 성인에서 중성지방/고밀도지단백콜레스테롤 비와 대사증후군 및 영양소 섭취와의 연관성 : 2016년 국민건강영양조사 자료를 이용하여)

  • Kim, Youngjon;Han, A Lum
    • Journal of Nutrition and Health
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    • v.52 no.3
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    • pp.268-276
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    • 2019
  • Purpose: Metabolic syndrome causes diabetes and increases the risk of cardiovascular disease. This study examined the correlation between metabolic syndrome, nutrition intake, and triglyceride (TG)/high-density lipoprotein (HDL) cholesterol ratio. Methods: Using the data from the $7^{th}$ KNHANES (2016), this study was conducted on healthy adults aged 19 and older. The components and existence of metabolic syndrome and nutrition intake were independent variables and the TG/HDLcholesterol ratio was a dependent variable. A complex sample logistic progress test was used with age, sex, smoking, and drinking frequency corrected. Results: The TG/HDLcholesterol ratio of people with metabolic syndrome was as high as 1.314 on average, compared to people without metabolic syndrome (p < 0.0001). Among each component of metabolic syndrome, the TG/HDL cholesterol ratio had a significant association with fasting blood glucose, TG, HDL cholesterol, and waist circumference (p < 0.05). Only energy and carbohydrate intake were significantly related to the TG/HDLcholesterol ratio (p < 0.05). Conclusion: The TG/HDLcholesterol ratio is associated with each component of metabolic syndrome, but in particular, it is positively correlated with the presence of metabolic syndrome. Lower energy intakehad a positive correlation with the TG/HDLcholesterol ratio. These results show that metabolic syndrome can be predicted using the TG/HDLcholesterol ratio, and a diet strategy through nutrition and health education is necessary to prevent metabolic syndrome.

Five Newly Collected Turnip Mosaic Virus (TuMV) Isolates from Jeju Island, Korea are Closely Related to Previously Reported Korean TuMV Isolates but Show Distinctive Symptom Development

  • Hu, Wen-Xing;Kim, Byoung-Jo;Kwak, Younghwan;Seo, Eun-Young;Kim, Jung-Kyu;Han, Jae-Yeong;Kim, Ik-Hyun;Lim, Yong Pyo;Cho, In-Sook;Domier, Leslie L;Hammond, John;Lim, Hyoun-Sub
    • The Plant Pathology Journal
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    • v.35 no.4
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    • pp.381-388
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    • 2019
  • For several years, temperatures in the Korean peninsula have gradually increased due to climate change, resulting in a changing environment for growth of crops and vegetables. An associated consequence is that emerging species of insect vector have caused increased viral transmission. In Jeju Island, Korea, occurrences of viral disease have increased. Here, we report characterization of five newly collected turnip mosaic virus (TuMV) isolates named KBJ1, KBJ2, KBJ3, KBJ4 and KBJ5 from a survey on Jeju Island in 2017. Full-length cDNAs of each isolate were cloned into the pJY vector downstream of cauliflower mosaic virus 35S and bacteriophage T7 RNA polymerase promoters. Their fulllength sequences share 98.9-99.9% nucleotide sequence identity and were most closely related to previously reported Korean TuMV isolates. All isolates belonged to the BR group and infected both Chinese cabbage and radish. Four isolates induced very mild symptoms in Nicotiana benthamiana but KBJ5 induced a hypersensitive response. Symptom differences may result from three amino acid differences uniquely present in KBJ5; Gly(382)Asp, Ile(891)Val, and Lys(2522)Glu in P1, P3, and NIb, respectively.

Factors and Their Correlation with Injury Severity of Elderly Pedestrian Traffic Accidents

  • Hyun, Tae gyu;Yeom, Seok-Ran;Park, Sung-Wook;Lee, Deasup;Kim, Hyung bin;Wang, Il Jae;Bae, Byung Gwan;Song, Min keun;Cho, Youngmo
    • Journal of Trauma and Injury
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    • v.32 no.3
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    • pp.143-149
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    • 2019
  • Purpose: No previous study has assessed elderly pedestrian traffic accidents based on a nationwide database. This study aimed to help primary physicians who examine patients in emergency departments to determine and make prompt and accurate treatment decisions. Methods: This study used data from the Emergency Department-based Injury Indepth Surveillance from 2013 to 2017, managed by the Korea Centers for Disease Control and Prevention. Pedestrians aged ${\geq}65years$ were included, and using multivariate logistic regression multiple factors were analyzed to determine their relationship with injury severity. Results: Of 227,695 subjects, 6,498 were included, of whom 2,065 (31.8%) were severely injured. There were more female than male patients in all severity groups. Most accidents occurred in the afternoon and on general roads. In the multivariate analysis, the odds ratio (OR) of injury severity for male pedestrians was 1.165 (95% confidence interval: 1.034-1.313, p=0.012). Older age of patients and the use of ambulances were associated with greater injury severity. The accident time affected the degree of injury severity; i.e., compared to dawn, injury severity increased in the morning (OR: 1.246, p=0.047) and decreased at night (OR: 0.678, p<0.001). A significant difference was noted in the correlation between the type of vehicle causing the accident and the accident severity; i.e., motorcycle accidents had lower severity than bicycle accidents (OR: 0.582, p=0.047). Conclusions: Injury severity was correlated with sex, age, transportation to the ED, TA onset time, and type of vehicle. The study results suggest that injury severity may be positively reflected in initial assessments and overall integrated treatments by physicians and in the related policies.

An Empirical Study on Firefighters' Health Hazard Factors -Focused on Fire Fighters, Rescue Workers and Emergency Medical Technicians Perception in Busan Fire Fighters- (소방공무원 건강장해 유해인자에 대한 실증연구 -화재진압대원, 구조대원, 구급대원의 인식조사를 중심으로-)

  • Kwon, Seol A;Lee, Min-Kyu;Park, Sang Ho;Kim, Da Young;Ryu, Sang Il
    • The Journal of the Korea Contents Association
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    • v.19 no.3
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    • pp.520-529
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    • 2019
  • This study is intended to provide basic data for health management of firefighters in the future by empirically looking into health hazard factors of firefighters in Busan City. It was revealed that firstly, the danger of harmful chemicals in a fire was perceived the most by firefighters, who extinguish a fire in person on the scene of a fire, and it was followed by the danger of falling while putting out a fire. This study is intended to provide basic data for health management of firefighters in the future by empirically looking into health hazard factors of firefighters in Busan City. It was revealed that firstly, the danger of harmful chemicals in a fire was perceived the most by firefighters, who extinguish a fire in person on the scene of a fire, and it was followed by the danger of falling while putting out a fire. Moreover, the danger of shift work was perceived the most by paramedics. This corresponds to the existing studies arguing that shift work is harmful to health. Next, the overload of patient transport was recognized as the second biggest hazard factor. This demonstrates they are worried about various second accidents that may happen due to a lot of patient transport works. In addition, the possibility of causing a traffic accident was perceived as a hazard factor too, since they must drive ambulance cars quickly to transport patients. Lastly, rescue workers regarded these hazard factors to be most dangerous. This is associated with their occupational characteristics, because rescue workers are the closest to diverse risks including a fire.

Correlation between Cytokine and Chemokine levels and Clinical Severity in Children with Mycoplasma pneumoniae Pneumonia

  • Choi, Hee Joung;Kim, Yeo Hyang
    • Pediatric Infection and Vaccine
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    • v.26 no.1
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    • pp.51-59
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    • 2019
  • Purpose: The aim of this study was to evaluate the relationships between cytokine and chemokine levels and the clinical severity of Mycoplasma pneumoniae pneumonia. Methods: A retrospective analysis of clinical and laboratory parameters were performed. Serum levels of interleukin (IL)-6, IL-8, IL-10, IL-18, interferon-${\gamma}$-inducible protein-10 (IP-10), macrophage inflammatory $protein-1{\beta}$, and tumor necrosis $factor-{\alpha}$ were measured. The severity of patients' clinical course and radiologic findings were also assessed. Results: Seventy-two patients (35 males and 37 females) with a median age of 3.9 years (range, 1-16 years) were enrolled. Patients with lobar pneumonia (n=29) had significantly higher C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-18 values than those with broncho-interstitial pneumonia (n=43). However, the cytokine and chemokine values did not differ between the group that was treated with corticosteroids (n=31) and the one that was not (n=41). The CRP, ESR, lactate dehydrogenase (LDH), IL-18, and IP-10 values showed positive correlations with fever duration prior to admission. The CRP and ESR values were positively correlated with IL-18, and LDH, with IP-10 levels. Conclusions: CRP, ESR, LDH, IL-18, and IP-10 values were associated with the severity of the disease, manifesting lobar pneumonia or prolonged fever duration prior to admission.

"Post-Decompressive Neuropathy": New-Onset Post-Laminectomy Lower Extremity Neuropathic Pain Different from the Preoperative Complaint

  • Boakye, Lorraine A.T.;Fourman, Mitchell S.;Spina, Nicholas T.;Laudermilch, Dann;Lee, Joon Y.
    • Asian Spine Journal
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    • v.12 no.6
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    • pp.1043-1052
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    • 2018
  • Study Design: Level III retrospective cross-sectional study. Purpose: To define and characterize the presentation, symptom duration, and patient/surgical risk factors associated with 'post-decompressive neuropathy (PDN).' Overview of Literature: PDN is characterized by lower extremity radicular pain that is 'different' from pre-surgical radiculopathy or claudication pain. Although it is a common constellation of postoperative symptoms, PDN is incompletely characterized and poorly understood. We hypothesize that PDN is caused by an intraoperative neuropraxic event and may develop early (within 30 days following the procedure) or late (after 30 days following the procedure) within the postoperative period. Methods: Patients who consented to undergo lumbar laminectomy with or without an instrumented fusion for degenerative lumbar spine disease were followed up prospectively from July 2013 to December 2014. Relevant data were extracted from the charts of the eligible patients. Patient demographics and surgical factors were identified. Patients completed postoperative questionnaires 3 weeks, 3 months, 6 months, and 1 year postoperatively. Questions were designed to characterize the postoperative pain that differed from preoperative pain. A diagnosis of PDN was established if the patient exhibited the following characteristics: pain different from preoperative pain, leg pain worse than back pain, a non-dermatomal pain pattern, and nocturnal pain that often disrupted sleep. A Visual Analog Scale was used to monitor the pain, and patients documented the effectiveness of the prescribed pain management modalities. Patients for whom more than one follow-up survey was missed were excluded from analysis. Results: Of the 164 eligible patients, 118 (72.0%) completed at least one follow-up survey at each time interval. Of these eligible patients, 91 (77.1%) described symptoms consistent with PDN. Additionally, 75 patients (82.4%) described early-onset symptoms, whereas 16 reported symptoms consistent with late-onset PDN. Significantly more female patients reported PDN symptoms (87% vs. 69%, p=0.03). Patients with both early and late development of PDN described their leg pain as an intermittent, constant, burning, sharp/stabbing, or dull ache. Early PDN was categorized more commonly as a dull ache than late-onset PDN (60% vs. 31%, p=0.052); however, the difference did not reach statistical significance. Opioids were significantly more effective for patients with early-onset PDN than for those with late-onset PDN (85% vs. 44%, p=0.001). Gabapentin was most commonly prescribed to patients who cited no resolution of symptoms (70% vs. 31%, p=0.003). Time to symptom resolution ranged from within 1 month to 1 year. Patients' symptoms were considered unresolved if symptoms persisted for more than 1 year postoperatively. In total, 81% of the patients with early-onset PDN reported complete symptom resolution 1 year postoperatively compared with 63% of patients with late-onset PDN (p=0.11). Conclusions: PDN is a discrete postoperative pain phenomenon that occurred in 77% of the patients who underwent lumbar laminectomy with or without instrumented fusion. Attention must be paid to the constellation and natural history of symptoms unique to PDN to effectively manage a self-limiting postoperative issue.

A Study on Psychological and Physical Health of Families of Victims One Year after the Sewol Ferry Disaster (세월호 재난 1년 후 유가족의 심리적, 신체적 건강에 대한 연구)

  • Ko, Jeong-Kyung;Han, Eunjin;Shin, Cheolmin;Lee, Seung-Hoon;Park, Sol A;An, Sora;Ko, Young-Hoon
    • Korean Journal of Psychosomatic Medicine
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    • v.26 no.2
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    • pp.179-187
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    • 2018
  • Objectives : The purpose of this study was to assess physical illnesses, psychological difficulties, and daily life function of victims' family members one year after the Sewol ferry disaster, in order to establish a basis of strategies to promote their mental health and resilience. Methods : We statistically analyzed self-reported data collected from a survey conducted between March 22 and 28, 2015 with 139 family members of victims. Results : All respondents complained about one or more psychological difficulties, and 95.4% of them had newly diagnosed or exacerbated physical illnesses. An increased number of psychological difficulties was associated with a greater tendency to present physical illnesses including chronic headache, gastrointestinal, musculoskeletal, obstetrico-gynecological, genitourinary, and cardiovascular disease. In addition, the majority of respondents reported a decrease in life functioning. Specifically, 71.9% reported interpersonal avoidance and 63.9% reported difficulty in returning to work. Conclusions : Not only psychological trauma but also physical illness and daily functioning should be evaluated in detail and actively addressed in the bereaved family members after a catastrophe.