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OBJECTIVES:: Global cerebral ischemia is a cause of poor prognosis after resuscitation from cardiac arrest. Various attempts have been made to minimize global cerebral ischemia but none been more effective than mild hypothermia induction. A few studies have shown the effect of mesenchymal stem cells on global cerebral ischemia, but no studies have compared this effect with mild hypothermia or assessed any possible interaction. We aimed to show the effect of mesenchymal stem cells on delayed neuronal death after global cerebral ischemia and to compare this effect with mild hypothermia. DESIGN:: Experimental study. SETTING:: Animal research laboratory. SUBJECTS:: Adult male Sprague-Dawley rats weighing 250–300 g. INTERVENTIONS:: Rats were subjected to 7 minutes of transient global cerebral ischemia and randomized into four groups: control, mild hypothermia, injection of human adipose-derived mesenchymal stem cells, and combined application of mild hypothermia and mesenchymal stem cells, along with four sham groups treated identically. Rats were euthanized 7 days after global cerebral ischemia. MEASUREMENTS AND MAIN RESULTS:: Degree of neuronal death in hippocampus was significantly higher in control than in other groups. The number of activated microglia was higher in control group than in other groups and was higher in mild hypothermia than shams, mesenchymal stem cells, mild hypothermia/mesenchymal stem cells. Degree of blood-brain barrier disruption and the count of infiltrated neutrophils were significantly higher in control than in other groups. Degree of oxidative injury was significantly higher in control than other groups. It was higher in mild hypothermia than sham groups, mesenchymal stem cells, mild hypothermia/mesenchymal stem cells and was higher in mesenchymal stem cells group than sham groups. Significantly, worse functional results were found in control than in other groups. CONCLUSIONS:: Administration of mesenchymal stem cells after transient global cerebral ischemia has a prominent protective effect on delayed neuron death, even compared with mild hypothermia. Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Park J.Y.,The Armed Forces Capital Hospital | Ahn R.S.,CHA Medical University
Psychoneuroendocrinology | Year: 2012

An exaggerated inflammatory process is considered an important pathophysiological feature of complex regional pain syndrome type 1 (CRPS-1). The hypothalamic-pituitary-adrenal (HPA) axis serves as a negative feedback mechanism for inflammatory processes. The present study examined the HPA axis function in patients with CRPS-1 by a determination of cortisol concentrations in saliva. Three sets of saliva samples were sequentially collected from 24 patients with CRPS-1 during medication (on-Med), 72. h after stopping medication (off-Med) and 8. h after the oral administration of 1. mg dexamethasone. One set of saliva samples was collected from healthy controls. The cortisol awakening response (CAR) and diurnal cortisol decline (DCD) were used as indices for HPA axis function. Cortisol levels during the post-awakening period in patients were increased following withdrawal of medications. The CAR during the off-Med condition was disappeared after administration of dexamethasone. Among the examined CRPS-related numerical variables, the frequency of spontaneous pain attacks showed relationships with the indices of HPA axis function. After classifying the patients into two subgroups, we observed that the CAR and DCD in patient who had a relatively high frequency of spontaneous pain attacks (subgroup 5≤) were lower and less steep than those in patient who had a relatively low frequency of spontaneous pain attacks (subgroup 0-4) for the on- and off-Med conditions. The CAR and DCD in subgroup 5≤ during their off-Med condition were comparable to those in controls. These results suggest that the increase in frequency of spontaneous pain attacks is associated with a reduced CAR and flattened DCD in patients CRPS-1. © 2012 Elsevier Ltd.

Kim H.J.,CHA Medical University
Molecules and cells | Year: 2010

The aim of this study was to understand the mechanisms that allow mSSC lines to be established from SSCs. Small, multilayer clumps of SSCs formed during two to four weeks of in vitro culture and were then transferred to MEF feeders. Small, round, monolayer colonies containing cells destined to convert to mSSCs, designated as intermediate state SSCs (iSSCs), first appeared after two to three passages. During an additional nine passages (47-54 days) under the same culture conditions, iSSCs slowly proliferated and maintained their morphology. Ultimately, a cell type with an ES-like morphology (mSSC) appeared from the iSSC colonies, and two mSSC cell lines were established. The mSSCs had a high proliferative potential in serum-free ES culture medium and have been successfully maintained since their first establishment (> 12 months). We also compared the specific characteristics of iSSCs with those of SSCs and mSSCs using immunocytochemistry, FACS, RT-PCR, DNA methylation, and miRNA analyses. The results suggest that iSSCs represent a morphologically distinct intermediate state with characteristic expression patterns of pluripotency-related genes and miRNAs that arise during the conversion of SSCs into mSSCs. Our results suggest that iSSCs could be a useful model for evaluating and understanding the initiation mechanisms of cell reprogramming.

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.

Lyu S.W.,CHA Medical University
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | Year: 2013

Basal luteinizing hormone (LH) levels have also been suggested to impact on ovarian responsiveness as well as basal follicular stimulating hormone (FSH) levels. The aim of this study was to compare the in vitro fertilization (IVF) outcomes according to cycle day 3 FSH/LH ratio and to assess the proper stimulation protocol between gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols. The retrospective cohort study recruited a total of 1211 women having the laboratory values of FSH (<10 IU/L) and LH within 3 months before IVF. Patients were treated with GnRH agonist long or GnRH antagonist protocols and stimulated with recombinant FSH (rFSH). The number of total retrieved oocytes and mature oocytes, implantation rate, clinical pregnancy rate and ongoing pregnancy rate were analyzed between groups: Group I: FSH/LH < 2 and Group II: FSH/LH ≥ 2. The Group II had the small number of retrieved oocytes and mature oocytes compared to the Group I (p = 0.000). Clinical and ongoing pregnancy rate were lower in Group II (p = 0.006, 0.006, respectively). In comparison of each protocol within groups, Group II showed significantly low pregnancy rate when GnRH antagonist was administered. In women with normal FSH level, high day 3 FSH/LH ratio can present subclinically low ovarian reserve and be predictive of lower pregnancy outcomes in fresh IVF cycles, and the choice of GnRH agonist can be related to favorable IVF outcomes.

Laparoscopic myomectomy (LM) has increased recently as treatment options for symptomatic uterine myomas for a patient who wants to preserve her uterus. However, adequate suture of the uterine defect is difficult in LM, even for an experienced surgeon. The most time-consuming step of LM is the suturing procedure. The suture material can tangle easily and disentanglement is time-consuming. We introduce a simple but highly effective instrument named "Puller" for continuous intracorporeal suturing in LM. After completion of myoma enucleation, the operator sutures the uterine defect with suture material in continuous manner. The tip of "Puller" looks like a hook. During the suture, the first assistant inserts the "Puller" on the suprapubic site and sets the suture material on the hook and pulls it extracorporeally. After one stitch, the operator pulls the suture material intracorporeally, and then the first assistant pulls the sutured portion of the thread extracorporeally with "Puller" and holds the stitch to maintain the adequate tension during the repair. From January 2011 to October 2011, 88 patients who were diagnosed with uterine myoma underwent LM using "Puller" by a single surgeon. The mean diameter of the myoma was 6.8 ± 2.1 cm, and multiple myomas were observed in 46 cases (52.3 %). As a result, the mean operation time was 65.0 ± 22.1 min, the estimated blood loss was 173.9 ± 179.8 ml. Mean weight of removed myoma was 141.5 ± 105.7 g. Postoperative febrile morbidity (body temperature higher than 37.7 °C) was observed in 15 patients (17 %). However, no patients had conversion to laparotomy and needed blood transfusion. There were no major complications that required reoperation or readmission. Laparoscopic myomectomy can be performed easily and effectively by using the "Puller" technique with standard instruments. Additionally, this "Puller" technique could be adopted in all minimally invasive surgery needed running suture for hemostasis and closure.

Jeong H.C.,CHA Medical University
Tuberculosis and Respiratory Diseases | Year: 2014

MicroRNAs (miRNAs) are a class of small noncoding RNAs that modulate target gene activity, and are aberrantly expressed in most types of cancer as well in lung cancer. A miRNA can potentially target a diverse set of mRNAs; further, it plays a critical role in lung tumorigenesis as well as affects patient outcome. Previous studies focused mainly on abnormal miRNAs expressions in lung cancer tissues. Interestingly, circulating miRNAs were identified in human plasma and serum in 2008. Since then, considerable effort has been directed to the study of circulating miRNAs as one of the bioniarkers of lung cancer. miRNAs expression of tissues and blood in lung cancer patients is being analyzed by more researchers. Recently, to overcome the high false-positivity of low-dose chest computed tomography scan, miRNAs in lung cancer screening are being investigated. This article summarizes the recent researches regarding clinical applications of miRNAs in the diagnosis and management of lung cancer. Copyright © 2014 The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

In general, the formation of embryoid bodies (EBs) is a commonly known method for initial induction of human embryonic stem cells (hESCs) into their derivatives in vitro. Despite the ability of EBs to mimic developmental processing, the specification and classifications of EBs are not yet well known. Because EBs show various differentiation potentials depending on the size and morphology of the aggregated cells, specification is difficult to attain. Here, we sought to classify the differentiation potentials of EBs by morphologies to enable one to control the differentiation of specific lineages from hESCs with high efficiency. To induce the differentiation of EB formation, we established floating cultures of undifferentiated hESCs in Petri dishes with hESC medium lacking basic fibroblast growth factor. Cells first aggregated into balls; ∼10 days after suspension culture, some different types of EB morphology were present, which we classified as cystic-, bright cavity-, and dark cavity-type EBs. Next, we analyzed the characteristics of each type of EB for its capacity to differentiate into the 3 germ layers via multiplex polymerase chain reaction (PCR), real-time PCR, and immunocytochemistry. Our results indicated that most cells within the cystic EBs were composed of endoderm lineage populations, and both of the cavity EB types were well organized with 3 germ-layer cells. However, the differentiation capacity of the bright cavity EBs was faster than that of the dark cavity EBs. Thus, the bright cavity EBs in this study, which showed equal differentiation tendencies compared with other types of EBs, may serve as the standard for in vitro engineering of EBs. These results indicate that the classification of EB morphologies allows the estimation of the differentiation status of the EBs and may allow the delineation of subsets of conditions necessary for EBs to differentiate into specific cell types.

Yoo J.H.,CHA Medical University
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi | Year: 2013

The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients. Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods. HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc. The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.

Park S.H.,CHA Medical University
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society | Year: 2013

Gastrointestinal or cardiovascular complications limit nonsteroidal anti-inflammatory drugs (NSAID) prescription. Glucosamine hydrochloride (GS-HCl) alternatively chosen, but debates still exist in its clinical efficiency. COX-2 instability through inhibiting COX-2 N-glycosylation of GS-HCl raised the possibility of NSAID sparing effect. Study was done to determine whether combination treatment of glucosamine and NSAID contributes to gastric safety through NSAID sparing effect. IEC-6 cells were stimulated with TNF-α and compared the expressions of inflammatory mediators after indomethacin alone or combination of indomethacin and GS-HCl by Western blotting and RT-PCR. C57BL/6 mice injected with type II collagen to induce arthritis were treated with indomethacin alone or combination of reduced dose of indomethacin and GS-HCl after 3 weeks. TNF-α increased the expression of COX-2, iNOS and inflammatory cytokines, but GS-HCl significantly attenuated TNF-α-induced COX-2 expression. Decreased COX-2 after GS-HCl was caused by N-glycosylation inhibition as much as tunicamycin. Combination of reduced dose of indomethacin and GS-HCl significantly reduced the expressions of ICAM-1, VCAM-1, IL-8, IL-1β, MMP-2, MMP-7, MMP-9, and MMP-11 mRNA as well as NF-κB activation better than high dose indomethacin alone. These NSAID sparing effect of GS-HCl was further proven in collagen-induced arthritis model. Combination of GS-HCl and 2.5 mg/kg indomethacin showed significant protection from gastric damages as well as efficacious anti-arthritic effect. Taken together, COX-2 N-glycosylation inhibition by GS-HCl led to indomethacin sparing effects, based on which combination of GS-HCl and reduced dose of NSAID can provide the strategy to secure stomach from NSAID-induced gastric damage as well as excellent anti-arthritic effects.

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