Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

Application of the Whole Genome-Based Bacterial Identification System, TrueBac ID, Using Clinical Isolates That Were Not Identified With Three Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Systems

BACKGROUND: Next-generation sequencing is increasingly used for taxonomic identification of pathogenic bacterial isolates. We evaluated the performance of a newly introduced whole genome-based bacterial identification system, TrueBac ID (ChunLab Inc., Seoul, Korea), using clinical isolates that were not identified by three matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems and 16S rRNA gene sequencing. METHODS: Thirty-six bacterial isolates were selected from a university-affiliated hospital and a commercial clinical laboratory. Species was identified by three MALDI-TOF MS systems: Bruker Biotyper MS (Bruker Daltonics, Billerica, MA, USA), VITEK MS (bioMérieux, Marcy l'Étoile, France), and ASTA MicroIDSys (ASTA Inc., Suwon, Korea). Whole genome sequencing was conducted using the Illumina MiSeq system (Illumina, San Diego, CA, USA), and genome-based identification was performed using the TrueBac ID cloud system (www.truebacid.com). RESULTS: TrueBac ID assigned 94% (34/36) of the isolates to known (N=25) or novel (N=4) species, genomospecies (N=3), or species group (N=2). The remaining two were identified at the genus level. CONCLUSIONS: TrueBac ID successfully identified the majority of isolates that MALDI-TOF MS failed to identify. Genome-based identification can be a useful tool in clinical laboratories, with its superior accuracy and database-driven operations.

Efficient Production of Murine Uterine Damage Model

BACKGROUND: Thin or damaged endometrium causes uterine factor-derived infertility resulting in a failure of embryonic implantation. Regeneration of endometrium is a major issue in gynecology and reproductive medicine. Various types of cells and scaffolds were studied to establish an effective therapeutic strategy. For this type of investigations, production of optimal animal models is indispensable. In this study, we tried to establish various murine uterine damage models and compared their features. METHODS: Three to ten-week-old C57BL/6 female mice were anesthetized using isoflurane. Chemical and mechanical methods using ethanol (EtOH) at 70 or 100% and copper scraper were compared to determine the most efficient condition. Damage of uterine tissue was induced either by vaginal or dorsal surgical approach. After 7-10 days, gross and microscopic morphology, safety and efficiency were compared among the groups. RESULTS: Both chemical and mechanical methods resulted in thinner endometrium and reduced number of glands. Gross morphology assessment revealed that the damaged regions of uteri showed various shapes including shrinkage or cystic dilatation of uterine horns. The duration of anesthesia significantly affected recovery after procedure. Uterine damage was most effectively induced by dorsal approach using 100% EtOH treatment compared to mechanical methods. CONCLUSION: Taken together, murine uterine damage models were most successfully established by chemical treatment. This production protocols could be applied further to larger animals such as non-human primate.

Deficiency of Anoctamin 5/TMEM16E causes nuclear positioning defect and impairs Ca²⁺ signaling of differentiated C2C12 myotubes

Anoctamin 5 (ANO5)/TMEM16E belongs to a member of the ANO/TMEM16 family member of anion channels. However, it is a matter of debate whether ANO5 functions as a genuine plasma membrane chloride channel. It has been recognized that mutations in the ANO5 gene cause many skeletal muscle diseases such as limb girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi muscular dystrophy type 3 (MMD3) in human. However, the molecular mechanisms of the skeletal myopathies caused by ANO5 defects are poorly understood. To understand the role of ANO5 in skeletal muscle development and function, we silenced the ANO5 gene in C2C12 myoblasts and evaluated whether it impairs myogenesis and myotube function. ANO5 knockdown (ANO5-KD) by shRNA resulted in clustered or aggregated nuclei at the body of myotubes without affecting differentiation or myotube formation. Nuclear positioning defect of ANO5-KD myotubes was accompanied with reduced expression of Kif5b protein, a kinesin-related motor protein that controls nuclear transport during myogenesis. ANO5-KD impaired depolarization-induced [Ca²⁺]i transient and reduced sarcoplasmic reticulum (SR) Ca²⁺ storage. ANO5-KD resulted in reduced protein expression of the dihydropyridine receptor (DHPR) and SR Ca²⁺-ATPase subtype 1. In addition, ANO5-KD compromised co-localization between DHPR and ryanodine receptor subtype 1. It is concluded that ANO5-KD causes nuclear positioning defect by reduction of Kif5b expression, and compromises Ca²⁺ signaling by downregulating the expression of DHPR and SERCA proteins.

Effect of Miscanthus sinensis var. purpurascens Flower Extract on Proliferation and Molecular Regulation in Human Dermal Papilla Cells and Stressed C57BL/6 Mice / 中国结合医学杂志

<p><b>OBJECTIVES</b>To investigate the hair growth-promoting effect of Miscanthus sinensis var. purpurascens (MSP) flower extracton on in vitro and in vivo models.</p><p><b>METHODS</b>MSP flower extract was extracted in 99.9% methanol and applied to examine the proliferation of human dermal papilla cells (hDPCs) in vitro at the dose of 3.92-62.50 μg/mL and hair growth of C57BL/6 mice in vivo at the dose of 1000 μg/mL. The expression of transforming growth factor β1 (TGF-β1), hepatocyte growth factor (HGF), β-catenin, substance P was measured by relative quantitative realtime polymerase chain reaction. Histopathological and immunohistochemical analysis were performed.</p><p><b>RESULTS</b>MSP (7.81 μg/mL) down-regulated TGF-β1 and up-regulated HGF and β-catenin in hDPCs (P<0.01). MSP (1000 μg/mL)-treated mice showed the earlier transition of hair follicles from the telogen to the anagen phase. The number of mast cells was lower in the MSP-treated mice than in other groups (P<0.05 vs. NCS group). Substance P and TGF-β1 were expressed in hair follicles and skin of the MSP group lower than that in negative control. Stem cell factor in hair follicles was up-regulated in the MSP-treated mice (P<0.01).</p><p><b>CONCLUSIONS</b>The MSP flower extract may have hair growth-promotion activities.</p>

Right Main Bronchus Rupture Presenting with Pneumoperitoneum

We report the case of a 16-year-old male patient who was involved in a traffic accident and transferred to the emergency department with mild chest pain. We initially did not find evidence of tracheal injury on computed tomography (CT). Within an hour after presentation, the patient developed severe dyspnea and newly developed subcutaneous emphysema and pneumoperitoneum were discovered. Abdominal CT showed no intra-abdominal injury. However, destruction of the right main bronchus was identified on coronal images of the initially performed CT scan. Emergency exploratory surgery was performed. The amputated right main bronchus was identified. End-to-end tracheobronchial anastomosis was performed, and the patient recovered without any complications.

Clinical assessment after human adipose stem cell transplantation into dogs

Adipose tissue-derived stem cell (ASCs) are an attractive source of stem cells with therapeutic applicability in various fields for regenerating damaged tissues because of their stemness characteristics. However, little has reported on evaluating adverse responses caused by human ASC therapy. Therefore, in the present study, a clinical assessment after human ASC transplantation into dogs was undertaken. A total of 12 healthy male dogs were selected and divided into four groups: saline infusion, saline bolus, ASC infusion, and ASC bolus groups. Physical assessment and blood analysis were performed following ASC transplantation, and the concentrations of angiogenic factors, and pro- and anti-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). There were no adverse vital sign responses among the dogs. Blood analyses revealed no remarkable complete blood count or serum chemistry results. ELISA results for angiogenic and anti-inflammatory factors including matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were significantly higher in the two ASCs groups than in the controls. In conclusion, this study demonstrated that transplantation of human ASCs produced no adverse effects and could be used safely in dogs. In addition, human ASCs could be involved in modulating secretions of angiogenic factors including MMP9, VEGF, bFGF, and HGF and anti-inflammatory factor IL-10.

Varicella Zoster Meningitis in an Immunocompetent Child / 대한소아신경학회지

Neurologic complications associated with varicella zoster virus (VZV) are rare in children. A 13-year-old boy was hospitalized due to headache, fever, and vomiting. Aseptic viral meningitis was strongly suspicious based on findings on physical exam, cerebrospinal fluid examination, and brain magnetic resonance imaging. On the second day of hospitalization, typical zosteriform rashes developed on his left chest wall across the T7-T8 dermatome. Tzanck test of the skin lesion was positive and polymerase chain reaction test for VZV was positive on the second cerebrospinal fluid examination. Serum immunoglobulin levels were within normal range. Intravenous acyclovir was started and symptoms and signs of meningitis gradually improved and the patient was discharged without any complications. In immunocompetent children, VZV meningitis is rare and requires rapid diagnosis and treatment. Therefore, it is necessary to prompt diagnosis and treatment thorough medical history, physical examination and laboratory examination.

Clinical Features of Herpes Zoster in Children according to Immune Status / 대한소아신경학회지

PURPOSE: Herpes zoster appears in all ages and its incidence progressively increase. It is more common in elderly people or immunocompromised people and can be accompanied by serious complications. This study was performed to investigate the clinical manifestation of herpes zoster according to immune status in children. METHODS: This study was retrospectively included 307 children under 18 years who were diagnosed and treated with herpes zoster at Inha University Hospital from 1997 to 2017 based on medical records. These patients were divided into two groups according to their immunity and their clinical features were compared. RESULTS: The mean age of the total 307 patients was 10.2 years, 151 (49.2%) in males. Eighty-seven patients were hospitalized and 220 patients were treated in an outpatient clinic. Most patients received antiviral treatment. The most common dermatomal distribution of the skin lesion was the thoracic region, followed by trigeminal, lumbar and sacral, cervical region. Twenty-one patients were immunocompromised and fifteen of them were hematologic disorders. Admission rate, history of chickenpox and mean duration of treatment were significantly higher in immunocompromised group (P < 0.05). There was no significant difference in age, dermatomal distribution and complication between the two groups. Complications were observed in 50 cases and more than half of them were zoster ophthalmicus. Another complication was Ramsay-Hunt syndrome, meningitis and skin infection. CONCLUSION: Immunocompromised patients had a longer duration of treatment and a higher history of chickenpox. The incidence of complications, dermatomal distribution and age did not differ from that of immunocompetent children.

Increased Frontal Gamma and Posterior Delta Powers as Potential Neurophysiological Correlates Differentiating Posttraumatic Stress Disorder from Anxiety Disorders

OBJECTIVE: Posttraumatic stress disorder (PTSD) is distinct from anxiety disorders in its etiology and clinical symptomatology, and was reclassified into trauma- and stressor-related disorders in DSM-5. This study aimed to find neurophysiological correlates differentiating PTSD from anxiety disorders using resting-state quantitative electroencephalography (qEEG). METHODS: Thirty-six patients with either PTSD or acute stress disorder and 79 patients with anxiety disorder were included in the analysis. qEEG data of absolute and relative powers and patients’ medication status on the day of qEEG examination were obtained. Electrodes were grouped into frontal, central, and posterior regions to analyze for regional differences. General linear models were utilized to test for group differences in absolute and relative powers while controlling for medications. RESULTS: PTSD patients differed from those with anxiety disorders in overall absolute powers [F(5,327)=2.601, p=0.025]. Specifically, overall absolute delta powers [F(1,331)=4.363, p=0.037], and overall relative gamma powers [F(1,331)=3.965, p=0.047] were increased in PTSD group compared to anxiety disorder group. Post hoc analysis regarding brain regions showed that the increase in absolute delta powers were localized to the posterior region [F(1,107)=4.001, p=0.048]. Additionally, frontal absolute gamma powers [F(1,107)=4.138, p=0.044] were increased in PTSD group compared to anxiety disorder group. CONCLUSION: Our study suggests increased overall absolute delta powers and relative gamma powers as potential markers that could differentiate PTSD from anxiety disorders. Moreover, increased frontal absolute gamma and posterior delta powers might pose as novel markers of PTSD, which may reflect its distinct symptomatology.

Comparison of Coronary Artery Bypass Graft-First and Percutaneous Coronary Intervention-First Approaches for 2-Stage Hybrid Coronary Revascularization

BACKGROUND: Hybrid coronary revascularization (HCR) was developed to combine the advantages of coronary artery bypass graft (CABG) with percutaneous coronary intervention (PCI). However, it is still controversial whether it is more optimal to perform CABG or PCI first. The purpose of this study was to compare the clinical outcomes of these 2 approaches. METHODS: Eighty patients who underwent HCR from May 2010 to December 2015 were enrolled in this retrospective analysis. The CABG-first group comprised 12 patients and the PCI-first group comprised 68 patients. Outcomes of interest included in-hospital perioperative factors, major adverse cardiac and cerebrovascular events (MACCEs), and the incidence of repeated revascularization, especially for the target vessel lesion. RESULTS: No significant difference was found in the amount of postoperative bleeding (p=0.239). The incidence of MACCEs was similar between the CABG-first and PCI-first groups (1 of 12 [8.3%] vs. 5 of 68 [7.4%], p>0.999). Repeated revascularization was performed on 3 patients (25%) in the CABG-first and 9 patients (13.2%) in the PCI-first group (p=0.376). CONCLUSION: There were no significant differences in postoperative and medium-term outcomes between the CABG-first and PCI-first groups. Based on these results, it can be inferred that it is safe to opt for either CABG or PCI as the primary procedure in 2-stage HCR.

Surgical Management of a Coronary-Bronchial Artery Fistula Combined with Myocardial Ischemia Revealed by ¹³N-Ammonia Positron Emission Tomography

A 71-year-old male with known bronchiectasis and atrial fibrillation was admitted to Seoul St. Mary's Hospital with recurrent transient ischemic attack. Radiofrequency ablation was performed to resolve the patient's atrial fibrillation, but failed. However, a fistula between the left circumflex artery and the bilateral bronchial arteries was found on computed tomography. Fistula ligation and a left-side maze operation were planned due to his recurrent symptom of dizziness, and these procedures were successfully performed. After the operation, the fistula was completely divided and no recurrence of atrial fibrillation took place. A coronary-bronchial artery fistula is a rare anomaly, and can be safely treated by surgical repair.

Tricuspid Papillary Fibroelastoma Mimicking Tricuspid Vegetation in a Patient with Severe Neutropenia

We report a 72-year-old male with known myelodysplastic syndrome who presented to the emergency department with a 7-day history of fever and dyspnea. Echocardiography revealed a round echogenic mass 13×16 mm in size attached to the atrial side of the tricuspid valve. Considering the high risk of infective endocarditis in the patient with a low absolute neutrophil count (130/mm3), emergency surgery was performed. Intraoperatively, a single gelatinous neoplasm was resected, and subsequent reconstruction of the involved leaflet was accomplished using autologous pericardium. The tumor was pathologically confirmed as papillary fibroelastoma with no evidence of infective endocarditis. Papillary fibroelastoma is a rare cardiac neoplasm that occurs in either the mitral or aortic valves. Interestingly, a few cases of tricuspid valve papillary fibroelastoma have been reported so far. Similar echocardiographic findings between vegetation and tricuspid valve neoplasm make it difficult to distinguish these two disease entities.

Extracorporeal Life Support in Patients with Hematologic Malignancies: A Single Center Experience

BACKGROUND: Extracorporeal life support (ECLS) in patients with hematologic malignancies is considered to have a poor prognosis. However, to date, there is only one case series reported in the literature. In this study, we compared the in-hospital survival of ECLS in patients with and without hematologic malignancies. METHODS: We reviewed a total of 66 patients who underwent ECLS for treatment of acute respiratory failure from January 2012 to December 2014. Of these patients, 22 (32%) were diagnosed with hematologic malignancies, and 13 (59%) underwent stem cell transplantation before ECLS. RESULTS: The in-hospital survival rate of patients with hematologic malignancies was 5% (1/22), while that of patients without malignancies was 26% (12/46). The number of platelet transfusions was significantly higher in patients with hematologic malignancies (9.69±7.55 vs. 3.12±3.42 units/day). Multivariate analysis showed that the presence of hematologic malignancies was a significant negative predictor of survival to discharge (odds ratio, 0.07; 95% confidence interval, 0.01–0.79); p=0.031). CONCLUSION: ECLS in patients with hematologic malignancies had a lower in-hospital survival rate, compared to patients without hematologic malignancies.

Bullae-Forming Pulmonary Metastasis from Choriocarcinoma Presenting as Pneumothorax

Gestational trophoblastic disease (GTD) is a condition of uncertain etiology, choriocarcioma, or placental-site hydatidiform moles, invasive moles, choriocarcinoma, and placental-site trophoblastic tumors. It arises from the abnormal proliferation of trophoblastic tissue and spreads beyond the uterus hematogenously. The early diagnosis of GTD is important to ensure timely and successful management and the preservation of fertility. We report the unusual case of a metastatic choriocarcinoma that formed bullae on the lung surface and presented as recurrent pneumothorax in a 38-year-old woman with elevated beta-human chorionic gonadotropin (hCG) levels. She underwent thoracoscopic wedge resection of the involved lung and four subsequent cycles of consolidation chemotherapy. No other evidence of metastatic disease or recurrent pneumothorax was noted during 22 months of follow-up. GTD should be considered in the differential diagnosis of spontaneous pneumothorax in reproductive-age women with an antecedent pregnancy and abnormal beta-hCG levels.

Postoperative Monitoring Following Jaw Surgery Is Essential

No abstract available.

The Level of Serum Immunoglobulin E Measured at General Hospitals in Six Regions of Korea in Children with Allergic Diseases / 소아알레르기및호흡기학회지

PURPOSE: We investigated the change in serum total immunoglobulin E (IgE) and allergen-specific IgE according to allergic diseases and age. METHODS: Allergic markers of children under 18 years of age with allergic diseases for the last 5 years were collected from 12 hospitals nationwide. The total data was 9,710. Data about levels of serum total IgE and allergen-specific IgE to 15 common allergens were collected. RESULTS: In children with asthma, serum total IgE was higher in older age than in younger age until age 7 to 12 years, at which time the level was highest (paper radioimmunosorbent test, 526.7 IU/mL; UniCAP, 339.9 IU/mL). The level was lower in older age than that during younger age. This change was similar to that in children with allergic rhinitis and atopic dermatitis. The level was highest at ages 7 to 12 years in children with allergic rhinitis, and at age 10 to 12 years in children with atopic dermatitis. In children with both asthma and allergic rhinitis, as well as in children with all three diseases, the change in serum total IgE was similar to that of children with an isolated disease. The highest level in children with all three diseases was higher than that in children with an isolated disease. The analysis of allergen-specific IgE positivity showed that food allergens were dominant before the age of 2 years, and that aeroallergens such as house dust mites were dominant. CONCLUSION: Serum total IgE in Korean children with allergic diseases was higher in older age than in younger age until the ages of 7 to 12 years, and then the change in total IgE by age was the opposite.

Abnormal Integrity of Corticocortical Tracts in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.

Diagnostic Performance of CT Colonography for the Detection of Colorectal Polyps

OBJECTIVE: To investigate the diagnostic value of CT colonography for the detection of colorectal polyps. MATERIALS AND METHODS: From December 2004 to December 2005, 399 patients underwent CT colonography and follow-up conventional colonoscopy. We excluded cases of advanced colorectal cancer. We retrospectively analyzed the CT colonography findings and follow-up conventional colonoscopy findings of 113 patients who had polyps more than 6 mm in diameter. Radiologists using 3D and 2D computer generated displays interpreted the CT colonography images. The colonoscopists were aware of the CT colonography findings before the procedure. RESULTS: CT colonography detected 132 polyps in 107 of the 113 patients and conventional colonoscopy detected 114 colorectal polyps more than 6 mm in diameter in 87 of the 113 patients. The sensitivity of CT colonography analyzed per polyp was 91% (41/45) for polyps more than 10 mm in diameter and 89% (101/114) for polyps more than 6 mm in diameter. Thirteen polyps were missed by CT colonography and were detected on follow-up conventional colonoscopy. CONCLUSION: CT colonography is a sensitive diagnostic tool for the detection of colorectal polyps and adequate bowel preparation, optimal bowel distention and clinical experience are needed to reduce the rate of missing appropriate lesions.

A case report about correction of implant position at horizontal plane after corticotomy