G protein-coupled receptors (GPCRs) are membrane receptors whose agonist-induced dynamic conformational changes trigger heterotrimeric G protein activation, followed by GRK-mediated phosphorylation and arrestin-mediated desensitization. Cytosolic regions of GPCRs have been studied extensively because they are direct contact sites with G proteins, GRKs, and arrestins. Among various cytosolic regions, the role of helix 8 is least understood, although a few studies have suggested that it is involved in G protein activation, receptor localization, and/or internalization. In the present study, we investigated the role of helix 8 in dopamine receptor signaling focusing on dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R). D1R couples exclusively to Gs, whereas D2R couples exclusively to Gi. Bioinformatic analysis implied that the sequences of helix 8 may affect GPCR-G protein coupling selectivity; therefore, we evaluated if swapping helix 8 between D1R and D2R changed G protein selectivity. Our results suggest that helix 8 is not involved in D1R-Gs or D2R-Gi coupling selectivity. Instead, we observed that D1R with D2R helix 8 or D1R with an increased number of hydrophobic residues in helix 8 relative to wild-type showed diminished β-arrestin-mediated desensitization, resulting in increased Gs signaling.
Arrestin ; Arrestins ; Computational Biology ; Cytosol ; Dopamine ; Family Characteristics ; GTP-Binding Proteins ; Membranes ; Phosphorylation ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Receptors, Dopamine

Yonsei Dermatology celebrated its centennial in 2017, marking 100 years since Kung Sun Oh established the first Department of Dermatology and Urology in Korea in 1917. Following the footsteps of Kung Sun Oh, a pioneer of Korean dermatology, its members united and worked to provide the best medical service and achieve academic milestones in dermatology. Over the past hundred years, Yonsei Dermatology has played a pivotal role in the advancement of medical science and academia in Korea. The main activities of the department include medical care, education, and dermatologic research. Its research activities have encompassed a wide spectrum of dermatologic manifestations from skin immunology and pathology to introduction of newly developed treatment technologies. As Kung Sun Oh was the first Korean professor of dermatology at Severance Medical School and a passionate educator, we continue to serve his will by nurturing medical students and dermatology specialists to serve as global medical leaders. The Kung Sun Oh Memorial Lecture, first hosted in 1977, was the beginning of mutual international academic exchange in the field of dermatology in Korea. The memorial lecture has played a major role in advancing the academic status of Korean dermatological science by inviting distinguished dermatologists from around the world as guest lecturers. Yonsei Dermatology has played a key role in the history of modern medicine and dermatology in Korea over the last 100 years and continues to make an impact.
Allergy and Immunology ; Dermatology* ; Education ; History, Modern 1601- ; Humans ; Korea* ; Pathology ; Schools, Medical ; Skin ; Solar System ; Specialization ; Students, Medical ; Urology

Porcine parvovirus 7 (PPV7) was first detected in Korean pig farms in 2017. The detection rate of PPV7 DNA was 24.0% (30/125) in aborted pig fetuses and 74.9% (262/350) in finishing pigs, suggesting that PPV7 has circulated among Korean domestic pig farms. Phylogenetic analysis based on capsid protein amino acid sequences demonstrated that the nine isolated Korean strains (PPV-KA1-3 and PPV-KF1-6) were closely related to the previously reported USA and Chinese PPV7 strains. In addition, the Korean strains exhibit genetic diversity with both insertion and deletion mutations. This study contributes to the understanding of the molecular epidemiology of PPV7 in Korea.
Aborted Fetus ; Agriculture ; Amino Acid Sequence ; Asian Continental Ancestry Group ; Capsid Proteins ; DNA ; Fetus ; Genetic Variation ; Humans ; Korea ; Molecular Epidemiology ; Parvovirus, Porcine ; Sequence Deletion ; Sus scrofa ; Swine

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

PURPOSE: To evaluate the effect of portal hypertension on the tumor recurrence in patients with hepatocellular carcinoma (HCC) and without hepatic decompression following radiofrequency ablation (RFA). MATERIALS AND METHODS: Treatment-naïve HCC patients within the Milan criteria and with Child-Pugh class A were included in this study, who had performed RFA in our hospital between January 2010 and March 2017. Univariate and multivariate analyses using the Cox proportional hazard model were performed to find the predictors of local or distant tumor recurrence. RESULTS: Overall, 178 patients were included in this study. Median follow-up period was 40.2 months. The difference in the local tumor progression rates depending on the absence or presence of portal hypertension was not statistically significant (p = 0.195). The 1-, 3-, and 5-year distant intrahepatic tumor spread rates were 6.6%, 29.5%, and 537% in patients without portal hypertension, and 23.4%, 51.9%, and 63.6% in patients with portal hypertension, respectively. The difference was statistically significant (p = 0.011). Univariate and multivariate analysis showed that portal hypertension was an independent predictor for distant intrahepatic tumor spread (p = 0.008). CONCLUSION For HCC patients with Child-Pugh class A, portal hypertension adversely affected distant intrahepatic tumor progression.

BACKGROUND/AIMS: It is unknown whether pulmonary rehabilitation (PR) is an effective intervention to manage coal-worker pneumoconiosis (CWP). We evaluated the efficacy and safety of an individualized PR program in 53 patients with CWP hospitalized in two medical institutions. METHODS: The PR program consisted of upper and lower extremity exercises to improve exercise endurance and skeletal musculoskeletal strength. All subjects performed treadmill and ergometer exercise with steady loading weights three times/week for 12 weeks. The following tests were performed before and after the study to investigate the efficacy of the PR program: modified Borg scale, pulmonary function test, mid-thigh circumference, maximum muscular strength, 6-min walk distance (6MWD), and the St. George's Respiratory Questionnaire (SGRQ), Korean version. RESULTS: Forty patients (75.5%) completed their PR programs. They improved significantly on the modified Borg scale, mid-thigh circumference, maximum muscular strength, 6MWD (all p < 0.000), and SGRQ (p = 0.007); however, no significant improvement was observed on the pulmonary function test. A significant improvement in dyspnea (p = 0.004) and 6MWD (p = 0.002) was observed in 12 patients with forced expiratory volume in 1 sec < 60%. The PR program with smoking cessation resulted in significantly more improvement on the 6MWD (p < 0.0001) and the SGRQ score (p = 0.002), as compared to those of patients who did not quit smoking. CONCLUSIONS: Our results show that an individualized 12-week PR program improves exercise capacity and quality of life for patients with CWP.
Dyspnea ; Exercise ; Exercise Therapy ; Forced Expiratory Volume ; Humans ; Lower Extremity ; Pneumoconiosis* ; Quality of Life ; Surveys and Questionnaires ; Rehabilitation* ; Respiratory Function Tests ; Smoke ; Smoking ; Smoking Cessation ; Weights and Measures

OBJECTIVES: The aim was to confirm the stem cell-like properties of the dental pulp stromal cells and to evaluate the morphologic changes during in vitro chondrogenesis. MATERIALS AND METHODS: Stromal cells were outgrown from the dental pulp tissue of the premolars. Surface markers were investigated and cell proliferation rate was compared to other mesenchymal stem cells. Multipotency of the pulp cells was confirmed by inducing osteogenesis, adipogenesis and chondrogenesis. The morphologic changes in the chondrogenic pellet during the 21 day of induction were evaluated under light microscope and transmission electron microscope. TUNEL assay was used to evaluate apoptosis within the chondrogenic pellets. RESULTS: Pulp cells were CD90, 105 positive and CD31, 34 negative. They showed similar proliferation rate to other stem cells. Pulp cells differentiated to osteogenic, adipogenic and chondrogenic tissues. During chondrogenesis, 3-dimensional pellet was created with multi-layers, hypertrophic chondrocyte-like cells and cartilage-like extracellular matrix. However, cell morphology became irregular and apoptotic cells were increased after 7 day of chondrogenic induction. CONCLUSIONS: Pulp cells indicated mesenchymal stem cell-like characteristics. During the in vitro chondrogenesis, cellular activity was superior during the earlier phase (within 7 day) of differentiation.
Adipogenesis ; Apoptosis ; Bicuspid ; Cartilage ; Cell Proliferation ; Chondrogenesis ; Dental Pulp ; Durapatite ; Electrons ; Extracellular Matrix ; In Situ Nick-End Labeling ; Light ; Mesenchymal Stromal Cells ; Osteogenesis ; Stem Cells ; Stromal Cells

VATER syndrome is defined as the combinations of three or more of the followings; Vertebral defect, Anal atresia, Esophageal atresia and/or Tracheo-Esophageal fistula, Renal dysplasia, and Radial-ray limb anomalies. A 21-month old female patient was admitted. She had the history of anastomosis of trcheo-esophageal fistula, V-P shunt operation due to hydrocephalus, and spina bifida. Upon admission, physical examinations showed increased deep tendon reflexes of all four extremities with grade 1 spasticity and popliteal angle being 45 degrees, bilaterally. The overall development of the patient was delayed. The imaging study showed hydrocephalus, periventricular leukomalatic change, underdevelopment of the cerebral cortex, atrophy of corpus callosum, Arnold-Chiary malformation, a vascular malformation along the intradural space from lower cervical to nearly entire thoracic vertebral level, multiple vertebral anomalies, and the fusion of multiple ribs. Furthermore hydronephrosis of the left kidney was detected. Follow-up of natural history and management of the patient is needed.
Anus, Imperforate ; Atrophy ; Cerebral Cortex ; Corpus Callosum ; Esophageal Atresia ; Esophagus ; Extremities ; Female ; Fistula ; Heart Defects, Congenital ; Humans ; Hydrocephalus ; Hydronephrosis ; Kidney ; Muscle Spasticity ; Natural History ; Physical Examination ; Radius ; Reflex, Stretch ; Ribs ; Spinal Dysraphism ; Spine ; Trachea ; Vascular Malformations

PURPOSE: To evaluate the incidence and clinical features of age-related macular degeneration (AMD) in Korea. METHODS: Web-based (www.armd-nova.or.kr) registration was conducted for AMD patients aged 50 or more who were newly diagnosed by retinal specialists in Korea from August 20, 2005 to August 20, 2006. Patient data including ophthalmologic examination, fundus photography, fluorescein angiogram and/or indocyanin green angiogram (ICG), past medical history, behavioral habit, combined systemic diseases were up-loaded. RESULTS: Among finally enrolled 1,141 newly diagnosed AMD patients, 690 patients (60.5%) were male and 451 patients (39.5%) were female. The average age of AMD patients was 69.7+/-8.0. Early AMD was observed in 190 patients and 951 patients had late AMD. Classic choroidal neovascular membrane (CNVM) was observed in 18.6% of exudative AMD patients and 63.4 % had occult CNVM. Subfoveal CNVM was observed in 80.4% of the patients with CNVM. Among the 580 exudative AMD eyes that performed indocyanin green angiography (ICG), 184 eyes (31.7%) had polypoidal choroidal vasculopathy (PCV) and 36 eyes (6.2%) showed retinal angiomatous proliferation (RAP). Age, male gender, smoking, diabetes and hypertension significantly increased the risk of the AMD among Koreans. CONCLUSIONS: Because of the low rate of participation by retinal specialists, definite incidence of AMD was not obtainable. However, the estimated 1-year AMD incidence in the Pusan area of Korea is at least 0.4%. In contrast to Western people, 31.7% of exudative AMD cases were revealed to be PCV and 6.2% were revealed to be RAP. This discrepancy between ethnic groups should be considered in the diagnosis and treatment modality selection of Korean AMD patients.
Aged ; Angiography ; Choroid ; Ethnic Groups ; Eye ; Female ; Fluorescein ; Humans ; Hypertension ; Incidence ; Korea ; Macular Degeneration ; Male ; Membranes ; Photography ; Retinaldehyde ; Smoke ; Smoking ; Specialization

BACKGROUND: Radiofrequency obliteration and endovenous laser therapy of the greater saphenous vein have recently been introduced as alternative, minimally invasive techniques for the treatment of saphenous vein incompetence. The 7 Fr. VNUS ClosureFAST(R) radiofrequency obliteration system was introduced in Gwang-Ju Veterans hospital. The purpose of this study is to evaluate the efficacy and complications of radiofrequency obliteration using the 7 Fr. VNUS ClosureFAST(R) system. MATERIAL AND METHOD: Between May 2, 2007 and May 31, 2008, we performed radiofrequency obliteration on 90 patients. The number of males was 67 and their mean age was 57.9+/-11.0 (range: 23~78) years old. The patients underwent follow up exams at 3 weeks after the procedures and then every 3 months. The effects of treatment and the complications were reviewed. RESULT: The postoperative complications were ecchymosis (94.4%), pain (27.8%), paresthesia (25.6%), bullous formation (8.9%), edema (6.7%) and phlebitis (2.2%). One patient showed good blood flow after 3 weeks and one patient showed good blood flow after 3 months. The one-year success rate of radiofrequency obliteration in varicose veins was 97.6%. CONCLUSION: Our data showed acceptable operative results and short-term clinical results for treating varicose veins with radio frequency obliteration. Long-term follow-up and comparison of radio frequency obliteration with high ligation and stripping, previous radiofrequency ablation and endovenous laser therapy are needed in the future.
Ecchymosis ; Edema ; Follow-Up Studies ; Hospitals, Veterans ; Humans ; Laser Therapy ; Ligation ; Male ; Paresthesia ; Phlebitis ; Postoperative Complications ; Saphenous Vein ; Varicose Veins ; Veins