1.Rapid generation of OPC-like cells from human pluripotent stem cells for treating spinal cord injury.
Dae Sung KIM ; Se Jung JUNG ; Jae Souk LEE ; Bo Young LIM ; Hyun Ah KIM ; Jeong Eun YOO ; Dong Wook KIM ; Joong Woo LEEM
Experimental & Molecular Medicine 2017;49(7):e361-
Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI. Here we demonstrate a rapid and efficient method to differentiate hPSCs into neural progenitors that retain the features of OPCs (referred to as OPC-like cells). We used cell sorting to select A2B5-positive cells from hPSC-derived neural rosettes and cultured the selected cells in the presence of signaling cues, including sonic hedgehog, PDGF and insulin-like growth factor-1. This method robustly generated neural cells positive for platelet-derived growth factor receptor-α (PDGFRα) and NG2 (~90%) after 4 weeks of differentiation. Behavioral tests revealed that the transplantation of the OPC-like cells into the spinal cords of rats with contusive SCI at the thoracic level significantly improved hindlimb locomotor function. Electrophysiological assessment revealed enhanced neural conduction through the injury site. Histological examination showed increased numbers of axon with myelination at the injury site and graft-derived myelin formation with no evidence of tumor formation. Our method provides a cell source from hPSCs that has the potential to recover motor function following SCI.
Animals
;
Axons
;
Behavior Rating Scale
;
Cues
;
Hedgehogs
;
Hindlimb
;
Humans*
;
Methods
;
Models, Animal
;
Myelin Sheath
;
Neural Conduction
;
Oligodendroglia
;
Platelet-Derived Growth Factor
;
Pluripotent Stem Cells*
;
Rats
;
Spinal Cord Injuries*
;
Spinal Cord*
2.Drug-Induced Anaphylaxis in a Single Korean Tertiary Hospital.
Il Joo MOON ; Hye Jung PARK ; Sung Ryeol KIM ; Beom Seok KOH ; Dong Woo LEEM ; Kyung Hee PARK ; Jae Hyun LEE ; Jung Won PARK
Korean Journal of Medicine 2015;88(3):281-287
BACKGROUND/AIMS: Drug-induced anaphylaxis (DIA) is a severe, acute, and potentially life-threatening condition. In Korea, only a few well-documented cases of DIA have been described. Therefore, the aim of this study was to investigate the clinical characteristics, causes, and management of DIA in a single Korean medical institute. METHODS: This was a retrospective medical record review of all DIA patients who visited the in-patient, out-patient, and emergency departments of our hospital from January 1 2006 to October 30 2013. RESULTS: Among 605 cases of anaphylaxis, 167 were drug-induced. The culprit drugs were contrast agents (43 cases, 25.7%), antibiotics (38, 22.8%), non-steroidal anti-inflammatory drugs (35, 21.0%), anti-cancer drugs (22, 13.2%), parenteral vitamins (9, 5.4%), ranitidine (6, 3.6%), and neuromuscular blockers (3, 1.8%). The most common organ-specific symptoms/signs were cardiovascular (74.3%), cutaneous (71.3%), respiratory (55.7%), and gastrointestinal manifestations (19.2%). In most cases, DIA was treated with antihistamines (77.2%) and systemic corticosteroids (76.5%); the use of epinephrine was considerably less frequent (35.3%). CONCLUSIONS: In our institution, contrast agents were the leading cause of DIA. Although epinephrine is the drug of choice in the treatment of acute anaphylaxis, fewer than 50% of the study patients received epinephrine to treat DIA.
Adrenal Cortex Hormones
;
Anaphylaxis*
;
Anti-Bacterial Agents
;
Contrast Media
;
Drug-Related Side Effects and Adverse Reactions
;
Emergency Service, Hospital
;
Epidemiology
;
Epinephrine
;
Histamine Antagonists
;
Humans
;
Korea
;
Medical Records
;
Neuromuscular Blockade
;
Neuromuscular Blocking Agents
;
Outpatients
;
Ranitidine
;
Retrospective Studies
;
Tertiary Care Centers*
;
Vitamins
3.Critical pathway of acute asthma attack for the Emergency Center: patients' outcomes and effectiveness.
Dong Woo LEEM ; Kyung Hee PARK ; Il Joo MOON ; Sung Ryeol KIM ; Beom Seok KOH ; Hye Jung PARK ; Jae Hyun LEE ; Jung Won PARK
Allergy, Asthma & Respiratory Disease 2015;3(1):30-34
PURPOSE: Early recognition and management of asthma attack is critical before it becomes worse. We developed critical pathway (CP) of asthma attack at Emergency Center (EC) for making undelayed decision and management of asthma attack. METHODS: Acute asthma attack assessment and treatment (4AT) CP began on April 1st 2012 and recruited the patients for 18 months. This study enrolled the patients who were older than 15 years and visited EC for dyspnea and wheezing. Initial assessment was done measuring peak expiratory flow rate (PEFR), oxygen saturation (SaO2). Once CP is activated, oxygen, inhalation of short acting beta2 agonist, and injection of corticosteroid were administered to the patients. Every hour after CP activated, we reassess the patients' response and make decisions whether to admit or discharge. RESULTS: Until January 10th 2014, 62 patients enrolled in this study. Seven patients hospitalized for asthma and 40 patients discharged. The other 15 patients were deactivated as they were diagnosed of heart failure, myocardial infarction, aortic dissection, anaphylaxis, chronic obstructive pulmonary disease and pneumonia for the causes of dyspnea. Mean Interval from EC arrival to 4AT activation was 32.6+/-29.1 minutes and the mean interval from 4AT activation to position decision was 254.5+/-302.0 minutes. Among 47 patients who were diagnosed with asthma attack, 13 patients were not aware of asthma before this attack. Forty patients were discharged at EC after management of CP. Among them, 34 patients revisited clinic, but 6 patients did not. We called back to the lost 6 patients but only 3 patients were connected. Even they visited EC due to asthma attack, 2 patients had no insight of importance of regular management and the other one promised to revisit. CONCLUSION: CP was successful for early management of asthma attack. However, 15% of discharged patients never show up again. So, education program about the importance of ongoing management of asthma for prevention of asthma attack is needed.
Anaphylaxis
;
Asthma*
;
Critical Pathways*
;
Dyspnea
;
Education
;
Emergencies*
;
Emergency Treatment
;
Heart Failure
;
Humans
;
Inhalation
;
Myocardial Infarction
;
Oxygen
;
Peak Expiratory Flow Rate
;
Pneumonia
;
Pulmonary Disease, Chronic Obstructive
;
Respiratory Sounds
4.A Case of Azathioprine Induced Warfarin Resistance in Behcet's Disease.
Sung Ryeol KIM ; Dong Woo LEEM ; Il Joo MOON ; Beom Seok KOH ; Myung Hee CHANG ; Jongha YOO ; Hee Chul YANG ; Chan Hee LEE
Journal of Rheumatic Diseases 2015;22(4):242-245
Behcet's disease is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Thrombosis associated with vascular inflammation in patients with Behcet's disease presents various clinical symptoms. Warfarin is usually administered for treatment of thrombosis. However, warfarin can interact with many medications that cause various problems. A 43-year-old woman with Behcet's disease presented with a swollen right leg. Deep vein thrombosis (DVT) was confirmed, and treated with warfarin. Due to exacerbation of Behcet's disease, she received azathioprine along with warfarin. Subsequently, the international normalized ratio (INR) decreased and DVT was exacerbated. Despite an increase in the warfarin dose, the patient did not reach the target INR. After discontinuation of azathioprine, DVT improved and the warfarin dose was decreased. There were no specific findings associated with a hypercoagulable status. This finding suggests the interaction of azathioprine and warfarin. Therefore, clinicians should be cautious regarding the possibility of drug interactions between azathioprine and warfarin.
Adult
;
Azathioprine*
;
Drug Interactions
;
Female
;
Humans
;
Inflammation
;
International Normalized Ratio
;
Leg
;
Skin
;
Stomatitis, Aphthous
;
Thrombosis
;
Ulcer
;
Uveitis
;
Venous Thrombosis
;
Warfarin*
5.Adverse drug reactions after taking the extract of Cudrania tricuspidata.
Beom Seok KOH ; Hye Jung PARK ; Sung Ryeol KIM ; Il Joo MOON ; Dong Woo LEEM ; Kyung Hee PARK ; Jae Hyun LEE ; Jung Won PARK
Allergy, Asthma & Respiratory Disease 2014;2(5):387-390
Cudrania tricuspidata is a deciduous tree belonging to the Moraceae plant, which has been widely used as a folk remedy or health supplements in the Asian countries including Korea. As far as we know, side effects from taking the extract of C. tricuspidata has not yet been reported. We reviewed the electronic medical records of 2 patients who had adverse drug reactions to C. tricuspidata. The first case was a 30-year-old woman without a specific medical history. She was admitted with a 2-week history of jaundice and dyspepsia after taking extract of C. tricuspidata for 3 days. Initial laboratory findings were as follows: aspartate aminotransferase, 364 IU/L; alanine aminotransferase, 574 IU/L; total bilirubin, 36.3 mg/dL; and direct bilirubin, 18.3 mg/dL. She was conservatively treated for liver and renal failure while awaiting liver transplantation. However, she was expired due to combined pneumonia and progressed hepatic and renal failure. The second case was a 42-year-old woman who has chronic urticaria without other medical history. She was admitted with a 3-month history of whole body rash with small pustular vesicle after taking extract of C. tricuspidata. She was treated with intravenous steroids and antihistamines. Skin lesions were improved after 1 week. Here, we report 2 cases of adverse drug reaction to C. tricuspidata. It should be considered that C. tricuspidata ingestion could cause severe adverse drug reactions such as liver failure and acute generalized exanthematous pustulosis.
Acute Generalized Exanthematous Pustulosis
;
Adult
;
Alanine Transaminase
;
Asian Continental Ancestry Group
;
Aspartate Aminotransferases
;
Bilirubin
;
Drug-Related Side Effects and Adverse Reactions*
;
Dyspepsia
;
Eating
;
Electronic Health Records
;
Exanthema
;
Female
;
Histamine Antagonists
;
Humans
;
Jaundice
;
Korea
;
Liver
;
Liver Failure
;
Liver Transplantation
;
Medicine, Traditional
;
Moraceae*
;
Plants
;
Pneumonia
;
Renal Insufficiency
;
Skin
;
Steroids
;
Trees
;
Urticaria
6.Gecko Proteins Exert Anti-Tumor Effect against Cervical Cancer Cells Via PI3-Kinase/Akt Pathway.
Ae Jin JEONG ; Chung Nam CHUNG ; Hye Jin KIM ; Kil Soo BAE ; Song CHOI ; Woo Jin JUN ; Sang In SHIM ; Tae Hong KANG ; Sun Hee LEEM ; Jin Woong CHUNG
The Korean Journal of Physiology and Pharmacology 2012;16(5):361-365
Anti-tumor activity of the proteins from Gecko (GP) on cervical cancer cells, and its signaling mechanisms were assessed by viable cell counting, propidium iodide (PI) staining, and Western blot analysis. GP induced the cell death of HeLa cells in a dose-dependent manner while it did not affect the viability of normal cells. Western blot analysis showed that GP decreased the activation of Akt, and co-administration of GP and Akt inhibitors synergistically exerted anti-tumor activities on HeLa cells, suggesting the involvement of PI3-kinase/Akt pathway in GP-induced cell death of the cancer cells. Indeed, the cytotoxic effect of GP against HeLa cells was inhibited by overexpression of constituvely active form of Akt in HeLa cells. The candidates of the functional proteins in GP were analyzed by Mass-spectrum. Taken together, our results suggest that GP elicits anti-tumor activity against HeLa cells by inhibition of PI3-kinase/Akt pathway.
Blotting, Western
;
Cell Count
;
Cell Death
;
HeLa Cells
;
Humans
;
Lizards
;
Phosphatidylinositol 3-Kinases
;
Propidium
;
Proteins
;
Uterine Cervical Neoplasms
7.Area-Based Occupational Disease Surveillance in Incheon, Korea: Results of an 11-year Data Survey.
Jeong Hoon KIM ; Shin Goo PARK ; Jong Han LEEM ; Jong Uk WON ; Sang Hwan HAN ; Soo Young CHUNG ; Sang Hoon KIM ; Hwan Cheol KIM ; Yun Chul HONG ; Cheol Woo KIM ; Chang Hwan KIM ; Dong Hyun KIM ; Dong Hoon LEE ; Seung Jun LEE ; Young Joong KANG ; Woo Seok KWAK ; Jeongbae RHIE
Korean Journal of Occupational and Environmental Medicine 2010;22(3):183-199
OBJECTIVES: Between Jan 1998 and Dec 2008, area-based occupational disease surveillance in Incheon was used to collect data on occupational diseases. The long-term data was used to estimate the scale of disease, to analyze disease characteristics, and to achieve surveillance in order to determine development tasks. METHODS: For a period of 11 years, occupation-related disease surveillance was performed on an annual basis for employees of Incheon industries. All cases of occupational disease were reported by means of the Incheon Occupational Disease Information Network (IODIN) web site, downloaded, and analyzed, subsequently. RESULTS: Between Jan 1998 and Dec 2008, 1577 cases of occupational disease were reported. Of these, there were 1043(66.1%) cases of occupational musculoskeletal disorders, 172(10.9%) cases of occupational asthma, 162(10.3%) cases of occupational dermatoses, 135(8.6%) cases of occupationally-related cancers, 30(1.9%) cases of pneumoconiosis, 27(1.7%) cases of toxic hepatitis, and 8(0.5%) cases of occupational neuronal disease. CONCLUSION: In the Incheon area, small and medium industries comprise 99% of business. The composition of the industry by category, in Incheon, is similar to the country on the whole. In actually, the data on occupational diseases in Korea are almost workers' compensation data. Thus, the survey of occupational disease based in Incheon, Korea, can serve as an estimate of the trends and size of the occupational disease throughout the entire country.
Asthma, Occupational
;
Commerce
;
Drug-Induced Liver Injury
;
Information Services
;
Korea
;
Neurons
;
Occupational Diseases
;
Pneumoconiosis
;
Skin Diseases
;
Workers' Compensation
8.Superior Cervical Sympathetic Ganglion Block may not Influence Early Brain Damage Induced by Permanent Focal Cerebral Ischemia in Rats.
Hyun Hae KIM ; Jeong Gill LEEM ; Jin Woo SHIN ; Ji Yeon SHIM ; Dong Myung LEE
The Korean Journal of Pain 2008;21(1):33-37
BACKGROUND: Cerebral blood vessels are innervated by sympathetic nerves from the superior cervical ganglion (SCG). The purpose of the present study was to evaluate the neuroprotective effect of superior cervical sympathetic ganglion block in rats subjected to permanent focal cerebral ischemia. METHODS: Thirty male Sprague-Dawley rats (270-320 g) were randomly assigned to one of three groups (control, lidocaine and ropivacaine). A brain injury was induced in all rats by middle cerebral artery occlusion with a nylon thread. The animals of the local anesthetic group received 30 microl of 2% lidocaine or 0.75% ropivacaine in the SCG. Neurologic scores were assessed 24 hours after brain injury. Brain samples were then collected. The infarct and edema ratios were measured by 2.3.5-triphenyltetrazolium chloride staining. RESULTS: There were no differences in the death rates, neurologic scores, or infarction and edema ratios between the three groups. CONCLUSIONS: These findings suggest that superior cervical sympathetic ganglion block may not influence the brain damage induced by permanent focal cerebral ischemia in rats.
Amides
;
Animals
;
Blood Vessels
;
Brain
;
Brain Injuries
;
Brain Ischemia
;
Edema
;
Ganglia, Sympathetic
;
Humans
;
Infarction
;
Infarction, Middle Cerebral Artery
;
Lidocaine
;
Male
;
Neuroprotective Agents
;
Nylons
;
Rats
;
Rats, Sprague-Dawley
;
Superior Cervical Ganglion
9.Concurrent FP (5-fluorouracil, cisplatin) Chemoradiotherapy for Patients with Esophageal Cancer.
Min Ok KIM ; Eui Sil HONG ; Ji Young CHAI ; Joung Muk LEEM ; Il Young YOU ; Won Dong KIM ; Woo Yoon PARK ; Seung Taik KIM ; Ki Hyeong LEE
Cancer Research and Treatment 2003;35(4):330-334
PURPOSE: The outcomes of a surgical approach for patients with an esophageal carcinoma remain unsatisfactory despite its high complication rates. We conducted a phase II trial, using combined FP (5-fluorouracil and cisplatin) chemotherapy and concurrent radiotherapy, as a definitive therapy for patients with esophageal cancer. MATERIALS AND METHODS: Patients with histologically proven esophageal cancer were enrolled onto this study. The treatment consisted of four courses of chemotherapy and six and a half weeks of radiotherapy. The patients received chemotherapy in weeks 1, 5, 12 and 16 (5-fluorouracil 1, 000 mg/m2 on days 1 to 4 and cisplatin 75 mg/m2 on day 1). Radiotherapy was administered at a dose of 59.4 Gy, in five 1.8 Gy fractions a week. RESULTS: A total of 22 eligible patients entered the study. Of the 19 evaluable patients, a complete response occurred in 7 (37%), and a partial response in 8 (42%). After a median follow-up of 35 months, the overall survival rate was 32% at three years and the median survival was 11 months. Fourteen (64%) received planned dose of radio-therapy and 13 (59%) received more than three courses of chemotherapy. However, there was no difference in three-year survival rates between the patients that received less than three courses of chemotherapy and those that received three or more courses (31% vs. 32%). The major treatment related toxicity was mucositis, which developed in every patient, with grades III or IV in thirteen (59%) patients. During the treatment, the patients lost, on average, 3.8% of their body weight. The mean hospital stay was 23 days, with a total duration of treatment of 74 days. CONCLUSIONS: Concurrent FP chemoradiotherapy was effective as a definitive therapy for patients with esophageal cancer. The major toxicity was mucositis. Although the treatment was relatively feasible, a randomized trial of reduced courses of chemotherapy is warranted.
Body Weight
;
Chemoradiotherapy*
;
Cisplatin
;
Drug Therapy
;
Esophageal Neoplasms*
;
Follow-Up Studies
;
Humans
;
Length of Stay
;
Mucositis
;
Radiotherapy
;
Survival Rate
10.Adrenergic sensitivity of uninjured C-fiber nociceptors in neuropathic rats.
Taick Sang NAM ; Dong Soo YEON ; Joong Woo LEEM ; Kwang Se PAIK
Yonsei Medical Journal 2000;41(2):252-257
We investigated the adrenergic sensitivity of afferent fibers in the L4 dorsal roots of rats with a unilateral ligation of the L5-L6 spinal nerves. About 12% of nociceptive fibers on the affected side were excited by sympathetic stimulation or by intra-arterial injection of norepinephrine which did not affect A beta-fiber activity. Sympathetic excitation of nociceptive fibers was suppressed by alpha 1-antagonist prazosin, while it was unaffected by alpha 2-antagonist yohimbine. Most of these fibers were excited by intra-arterial injection of alpha 1-agonist phenylephrine, without being affected by an injection of alpha 2-agonist clonidine. Sympathetic excitation was blocked by lidocaine applied near the receptive fields of recorded fibers. The results suggested that some nociceptors remaining intact after partial nerve injury become sensitive to sympathetic activity by the mediation of alpha 1-adrenoceptors in the peripheral endings.
Animal
;
Male
;
Nerve Fibers/physiology*
;
Nociceptors/physiology*
;
Norepinephrine/pharmacology
;
Pain/physiopathology*
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Adrenergic, alpha-1/physiology*

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