The deacetylase HDAC6 is an essential component of stress granules and plays a critical role in the cellular response to stress

The reversible acetylation of histones has a critical role in transcriptional regulation. Likewise reversible acetylation of non-histones proteins is also important for other cellular processes. Acetylation and deacetylation of histones and other proteins are catalyzed by opposing histone acetyl transferases (HATs) and deacetylases (HDACs) respectively. Among three classes of histone deacetylases, HDAC6 is a very unique class II HDAC enzyme which possesses two independent deacetylase domains and a Zn-UBP ubiquitin binding domain at the C-terminus. HDAC6 has been shown to interact with nuclear proteins as well as cytoplasmic proteins such as tubulin and HSP90. However, the physiological function of HDAC6 is not fully understood yet. Therefore, to further define the cellular function of HDAC6, an identification of novel interacting proteins has been undertaken. The first section of this thesis describes the identification of one novel HDAC6 interacting protein and the role of HDAC6 in stress granule (SG) formation in response to environmental stress. First of all, we identified new HDAC6 interacting proteins using proteomic affinity trap approach. Here, we focused that HDAC6 interacts and colocalizes with a previously identified stress granule component, G3BP (RasGAP associated endoribonuclease) in vitro and in vivo. We first discovered that HDAC6 is a stable and critical component of stress granules. Further experimental data suggested that HDAC6 can regulate the assembly of SGs via recruiting SG components to the microtubule system. Because of this HDAC6 may have an impact on various processes involoving RNA metabolism and we provide initial evidence that the miRNA pathway is indeed influenced by HDAC6 function. The second section of this thesis examines the role of HDAC6 in response to various stresses. The involvement of HDAC6, a multi-functional cytoplasmic deacetylase, in processes such as the clearance of cytotoxic aggregated misfolded proteins and the deacetylation of HSP90 chaperone, has prompted us to investigate a role for HDAC6 in cellular protection under stress condition. In hypoxia, HDAC6 regulated stability of HIF- 1α by controlling its deacetylation. Indeed, loss of HDAC6 rendered cells more sensitive to programmed cell death. Moreover, depletion of HDAC6 affected the recovery of cells from stress as well as the direct stress response, suggesting a significant role of HDAC6 as a cellular regulator of the stress response. In addition, a number of other putative HDAC6 interactors are presented, which were identified in the initial mass spectrometry screens. Several of these proteins encode cytoplasmic factors that have a role in RNA metabolism, protein translation or in cytoskeletal regulation. Therefore, it appears likely that at least some of these may turn out to be relevant partners contributing to HDAC6 function

Recognition of Transmembrane Protein 39A as a Tumor-Specific Marker in Brain Tumor

Transmembrane protein 39A (TMEM39A) belongs to the TMEM39 family. TMEM39A gene is a susceptibility locus for multiple sclerosis. In addition, TMEM39A seems to be implicated in systemic lupus erythematosus. However, any possible involvement of TMEM39A in cancer remains largely unknown. In the present report, we provide evidence that TMEM39A may play a role in brain tumors. Western blotting using an anti-TMEM39A antibody indicated that TMEM39A was overexpressed in glioblastoma cell lines, including U87-MG and U251-MG. Deep-sequencing transcriptomic profiling of U87-MG and U251-MG cells revealed that TMEM39A transcripts were upregulated in such cells compared with those of the cerebral cortex. Confocal microscopic analysis of U251-MG cells stained with anti-TMEM39A antibody showed that TMEM39A was located in dot-like structures lying close to the nucleus. TMEM39A probably located to mitochondria or to endosomes. Immunohistochemical analysis of glioma tissue specimens indicated that TMEM39A was markedly upregulated in such samples. Bioinformatic analysis of the Rembrandt knowledge base also supported upregulation of TMEM39A mRNA levels in glioma patients. Together, the results afford strong evidence that TMEM39A is upregulated in glioma cell lines and glioma tissue specimens. Therefore, TMEM39A may serve as a novel diagnostic marker of, and a therapeutic target for, gliomas and other cancers

Hepatitis B surface antigen levels at 6 months after treatment can predict the efficacy of lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B

Background/AimsQuantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy.MethodsLMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment.ResultsFifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020).ConclusionsThe HBsAg level at 6 months after treatment can help predict treatment response

Congenital and multiple hobnail hemangiomas

Hobnail hemangioma (targetoid hemosiderotic hemangioma) is a vascular tumor affecting the limbs or trunk. Characteristically, the lesion has a "targetoid" clinical feature and dilated vascular spaces lined by hobnail endothelial cells at histologic examination. The age of onset is widely variable, form 5~67 years, typically occurring in young or middle-aged persons. It is usually apparent as a small solitary lesion. However, multiple lesions are identified sometimes. Herein, we report two cases of hobnail hemangioma in 7-year-old and 15-year-old males. Of note, the former case had a congenital lesion and the latter, multiple acquired lesions, which are both rare atypical presentations of the disease.OAIID:oai:osos.snu.ac.kr:snu2011-01/102/2008000790/11SEQ:11PERF_CD:SNU2011-01EVAL_ITEM_CD:102USER_ID:2008000790ADJUST_YN:NEMP_ID:A079501DEPT_CD:801CITE_RATE:.531FILENAME:hobnail hemangiomas.pdfDEPT_NM:의학과SCOPUS_YN:NCONFIRM:

Outcome prediction of pediatric drowning

Purpose Despite the well-known mortality of pediatric drowning, there is a paucity of evidence on the implications of an initial evaluation on the relevant outcome of drowning. This study aimed to investigate the association of initial clinical findings with outcome of children undergoing drowning. Methods This retrospective study was conducted using the medical records of 56 children undergoing drowning who visited 3 Korean academic hospitals from January 2000 through May 2020. We analyzed information regarding the prehospital resuscitation, drowning time, a 4-tiered chest radiographic grade, and the baseline characteristics. The grade was defined based on the findings of initial chest radiographs. The poor outcomes were defined as the need for intensive care unit care or death aftercare. We analyzed the association of the prehospital resuscitation, submersion time, and the radiographic grade with the poor outcomes using binary logistic regression. Results Among the 56 children, 31 (55.4%) were aged 1-4 years. Prehospital resuscitation and 1-5 minutes of submersion time were noted in the 25 (44.6%) and 30 children (53.6%), respectively. The chest radiographic grades 1 through 4 accounted for 17 (30.4%), 20 (35.7%), 12 (21.4%), and 3 children (5.4%), respectively. Poor outcomes occurred in 17 children (30.4%), including 3 deaths (5.4%). The association with the poor outcomes was noted in the submersion time of longer than 5 minutes (adjusted odds ratio, 21.49; 95% confidence interval, 1.11-415.73; compared with < 1 minute) while not in the submersion time and chest radiographic grade. Conclusion This study confirms that submersion time is an outcome predictor of drowning

Effect of Guizhifulingwan (Keishibukuryogan) on climacteric syndrome: study protocol for a randomized controlled pilot trial

SPIRIT 2013 checklist. (DOCX 51 kb

Congenital Atrophoderma of Pasini and Pierini

Idiopathic atrophoderma of Pasini and Pierini is a form of dermal atrophy of unknown etiology, usually affecting women during their adolescence and young adulthood. A 2-yr-old girl was presented with erythematous atrophic lesion on the right shoulder, which appeared from birth. The histologic findings were consistent with atrophoderma. This patient, to the best of our knowledge, is the first case of atrophoderma with an onset since birth

The difference of Use of CT in the general versus pediatric emergency departments for adolescent patients in the same tertiary hospital

Objective The use of computed tomography (CT) in pediatric patients has decreased since the association between radiation and cancer risk has been reported. However, in adolescent patients being treated as adult patients, there has been a high incidence of CT use in emergency departments (EDs). Thus, this study aimed to evaluate the CT use in adolescent patients with complaints of headache or abdominal pain in the general and pediatric EDs of the same hospital. Methods A retrospective chart review of patients aged 15 to 18 years, who presented with headache or abdominal pain at the general and pediatric EDs of Seoul National University Hospital from January 2010 to December 2014, was conducted. Results A total of 407 adolescent patients with complaints of headache and 980 with abdominal pain were included in this study. The adolescent patients in the general ED were more likely to undergo CT scans than those in the pediatric ED, with both patients having headache (42.4% vs. 20.5%, respectively, P<0.001) and abdominal pain (29.0% vs. 18.4%, respectively, P<0.001). There was no statistical difference in the rates of positive CT findings between the general and pediatric EDs. The frequency of visits to the general ED was associated with high rates of CT use in adolescent patients with complaints of headache (odds ratio, 3.95; 95% confidence interval, 2.01 to 7.77) and those with abdominal pain (odds ratio, 1.76; 95% confidence interval, 1.18 to 2.64). Conclusion The ED setting influences the use of CT on adolescent patients, and a child-friendly environment could reduce the radiation risks

HBsAg level and clinical course in patients with chronic hepatitis B treated with nucleoside analogue: five years of follow-up data

Background/AimsQuantification of the hepatitis B surface antigen (HBsAg) is increasingly used to determine the treatment response in patients with chronic hepatitis B (CHB). However, there are limited data about the clinical implications of Quantification of HBsAg long-term nucleoside analogue treatment for CHB. We investigated the clinical correlation between HBsAg level and clinical course in patients with CHB who are treated long-term with nucleoside analogues.MethodsPatients with CHB who started lamivudine or entecavir monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at 6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between the groups according to the presence or absence of a virological response (VR) and resistance.ResultsForty-eight patients were analyzed. There was no definite reduction in HBsAg level during the early period of treatment; differences in HBsAg levels between baseline and each time point were significant only at 5 years (P=0.028). In a subgroup analysis, this difference was significant only in non-resistant patients at 5 years (P=0.041).ConclusionsThere was no definite decrease in the HBsAg level during the early period of nucleoside analogue treatment, with long-term treatment being required to observe a significant reduction

Insulin Fact Sheet in Type 1 and 2 Diabetes Mellitus and Trends of Antidiabetic Medication Use in Insulin Users with Type 2 Diabetes Mellitus: 2002 to 2019

Background This study investigated the trends of insulin use among Korean patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Changes in prescription of antidiabetic medications in T2DM patients taking insulin therapy were evaluated. Methods We analyzed data from the National Health Insurance Service database in Korea to evaluate the prevalence of insulin users and trends of insulin use in T1DM and T2DM patients from January 2002 to December 2019. We also investigated numbers and types of antidiabetic medications in insulin users with T2DM. Results The overall total number of insulin users increased from 2002 to 2019, reaching 348,254 for T2DM and 20,287 for T1DM in 2019 compared with 109,974 for T2DM and 34,972 for T1DM in 2002. The proportion of patients using basal analogs and short acting analogs have increased and those using human insulin, premixed insulin, or biphasic human insulin have decreased (rapid acting analogs: 71.85% and 24.12% in T1DM and T2DM, respectively, in 2019; basal analogs: 76.75% and 75.09% in T1DM and T2DM, respectively, in 2019). The use of other antidiabetic medication in addition to insulin increased for T2DM, especially in dual therapy, reaching up to 52.35% in 2019 compared with 16.72% in 2002. Conclusion The proportion of the patients using basal or rapid acting analogs increased among all insulin users in both T1DM and T2DM patients. Among patients with T2DM, the proportion of patients using antidiabetic medications in addition to insulin was significantly increased compared to those who used insulin alone