1.Angiogenesis and Signal Trasduction.
Young Mi KIM ; Young Myoung KIM ; Jong Dae KIM ; Young Guen KWON
Journal of Korean Society of Endocrinology 2001;16(3):284-292
No abstract available.
2.New Method for Wound Healing Using V.A.C.(Vacuum-assisted Closure).
Jeong Guen HONG ; Do Myung CHANG ; Paik Kwon LEE ; Young Jin KIM
Journal of the Korean Society of Plastic and Reconstructive Surgeons 1999;26(5):1082-1086
Healing is an intricate, interdependent process that involves complex interactions between cells, the microcellular environment, biochemical mediators and extracellular matrix molecules. The goals of wound healing are to minimize bloods loss, to replace any defect with new tissue, and to restore an intact epithelial barrier as rapidly as possible. The rate of wound healing is limited by the available vascular supply and the rate of formation of new capillaries and matrix molecules, which are heavily influenced by locally-acting growth factors that affect proliferation, angiogenesis, chemotaxis, gene expression, proteinases, and protein production. We present a new method for wound control and treatment, the V.A.C (vacuum-assisted closure) technique. It places open-cell foam dressing into the wound cavity and applies subatmospheric pressure. The application of subatmospheric pressure accelerates the rate of wound healing by the foollowing two mechanisms: 1. Removal of excessive interstitial fluids, which decrease localized edema, reduce concentration of inhibitory factors, and increase local blood flow. 2. Transmission of mechanical forces to surrounding tissues with resultant deformation of the extracellular matrix and cells, which then increase protein and matrix synthesis as well as cell proliferation. We applied it to 17 patients: 1 Livedo vasculitis, 1 burned by flame 3 pressure sores, 1 extravasation injury, 1 wound infection, 2 wound disruption, and 8 diabetes mellitus feet. In the end, most of the remaining wounds were treated with a simple split-thickness skin graft and the results were encouraging. We concluded that the V.A.C technique may be an effective substitute to help promote wound healing. It could be especially helpful in chronic complicated wounds in aging or debilitated patients who can not tolerate aggressive surgical procedures.
Aging
;
Bandages
;
Burns
;
Capillaries
;
Cell Proliferation
;
Chemotaxis
;
Diabetes Mellitus
;
Edema
;
Extracellular Fluid
;
Extracellular Matrix
;
Foot
;
Gene Expression
;
Humans
;
Intercellular Signaling Peptides and Proteins
;
Peptide Hydrolases
;
Pressure Ulcer
;
Skin
;
Transplants
;
Vasculitis
;
Wound Healing*
;
Wound Infection
;
Wounds and Injuries*
3.A Case of Retrograde Jejunojejunal Intussusception into the Braum Anastomosis after Billroth II Operation.
Byung Suk PARK ; Hyung Guen LEE ; Young Seok PARK ; Oh Jung KWON ; Sung Joon KWON ; Kyu Young JUN
Journal of the Korean Surgical Society 1997;52(3):446-450
N/AA case of retrograde intussusception of efferent limb into Braun side-to-side jejunojenunal anastomosis after gastric surgery is presented. Intussusception is an uncommon and well-recognized complication after gastric surgery. A 60-year old female was admitted to Hanyang University Hospital with a chief complaint of epigastric pain and hematemesis of 6 hours duration. Patient had a history of distal gastrectomy with gastrojejunostomy due to early gastric cancer(Stage I) 3 years ago. Emergency abdominal CT revealed jejunojejunal intussusception into Braun anastomosis. Exploration and segmental resection of jejunum with end-to-end reanastomosis were performed.
Emergencies
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Extremities
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Female
;
Gastrectomy
;
Gastric Bypass
;
Gastroenterostomy*
;
Hematemesis
;
Humans
;
Intussusception*
;
Jejunum
;
Middle Aged
;
Tomography, X-Ray Computed
4.Hhip regulates tumor-stroma-mediated upregulation of tumor angiogenesis.
Vijayendra AGRAWAL ; Dong Young KIM ; Young Guen KWON
Experimental & Molecular Medicine 2017;49(1):e289-
Tumor growth is governed by the coordinated action of various types of cells that are present in the tumor environment. Fibroblasts, which constitute a major fraction of the stroma, participate actively in various signaling events and regulate tumor development and metastasis. The Hedgehog (Hh) pathway plays an important role in promoting tumor malignancy via fibroblasts; however, the role of hedgehog interacting protein (hhip; inhibitor of Hh pathway) in tumor growth is poorly understood. Here we implanted B16F10 tumors in hhip+/− mice to study the tumor growth characteristics and the vascular phenotype. Furthermore, the mechanism involved in the observed phenomena was explored to reveal the role of hhip in tumor growth. The tumors that were implanted in hhip+/− mice exhibited accelerated growth and increased tumor angiogenesis. Although we observed a decrease in hypoxia, blood vessels still had abnormal phenotype. We found that increased Hh signaling in tumor fibroblasts induced a high expression of vascular endothelial growth factor (VEGF), which subsequently resulted in an increased proliferation of endothelial cells. Thus, the heterozygous knockdown of hhip in mice could affect Hh signaling in tumor fibroblasts, which could cause the increased production of the growth factor VEGF. This signaling, via a paracrine effect on endothelial cells, increased tumor vascular density.
Animals
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Anoxia
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Blood Vessels
;
Endothelial Cells
;
Fibroblasts
;
Hedgehogs
;
Mice
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Neoplasm Metastasis
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Phenotype
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Up-Regulation*
;
Vascular Endothelial Growth Factor A
5.Computational Analysis of Tumor Angiogenesis Patterns Using a Two-dimensional Model.
Eun Bo SHIM ; Young Guen KWON ; Hyung Jong KO
Yonsei Medical Journal 2005;46(2):275-283
Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.
Computer Simulation
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Fibroblast Growth Factor 2/metabolism
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Humans
;
*Models, Biological
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Neoplasms/*blood supply/metabolism
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Neovascularization, Pathologic/*physiopathology
;
Research Support, Non-U.S. Gov't
6.Clinical Characteristics of Walnut Allergy and Evaluation of Cross-Reactivity between Walnut and Peanut in Children Under 4 Years of Age.
Jeong Min LEE ; Eun Jin KIM ; Duck Guen KWON ; Soo Young LEE
Pediatric Allergy and Respiratory Disease 2011;21(4):261-268
PURPOSE: Walnut (WN) allergy in young children has rarely been reported in Asia. This study focused on the clinical characteristics of WN allergy, co-sensitization, and cross-reactivity between WN and peanut (PN) in young Korean children. METHODS: This study was based on a data analysis of 22 patients, all under the age of 4 years, who were diagnosed with allergic disease at Ajou University Hospital from January 2009 to December 2010. They were suspected to have a WN allergy or needed a screening examination to exclude food allergy. Sera from all children were analyzed for PN-, WN-, and pine nut-specific immunoglobulin E (IgE) (ImmunoCAP). Clinical details, feeding, and familial history of patients were collected by medical history. Additionally, we produced WN, PN, and pine nut extracts, and sera were tested with an enzyme linked immunosorbentassay inhibition test. RESULTS: The subjects were 16 male and 6 female with a median aged of 24 months. Ten of 22 had a definite history of WN exposure. Among them, two (4.28 kU/L, 11.1 kU/L) were diagnosed with anaphylaxis, four (7.34 to 27.4 kU/L) were diagnosed with angioedema, and four (1.35 to 3.17 kU/L) were diagnosed with urticaria. We confirmed that PN in the IgE-ELISA was profoundly inhibited by the WN extract. CONCLUSION: This study identified multiple cases of WN allergy in young children in Korea, indicating that it is not rare. Co-sensitization and clinical adverse reactions between PN and WN suggests that more investigations are needed to conclude cross-reactivity between PN and WN.
Aged
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Anaphylaxis
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Angioedema
;
Asia
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Child
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Female
;
Food Hypersensitivity
;
Humans
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Hypersensitivity
;
Immunoglobulin E
;
Immunoglobulins
;
Juglans
;
Korea
;
Male
;
Mass Screening
;
Nuts
;
Statistics as Topic
;
Urticaria
7.Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production.
Seon Jin LEE ; Seung NAMKOONG ; Kwon Soo HA ; Woo Dong NAM ; Young Guen KWON ; Hansoo LEE ; Eun Young YOON ; Dong Jo CHANG ; Soon Ok KIM ; Young Myeong KIM
Experimental & Molecular Medicine 2007;39(2):230-238
Colchicine has been shown to regulate the expression of inflammatory gene, but this compound possesses much weaker anti-inflammatory activity. In this study, we synthesized a new colchicine derivative CT20126 and examined its immunomodulatory property. CT20126 was found to have immunosuppressive effects by inhibiting lymphocyte proliferation without cytotoxicity and effectively inhibit the transcriptional expression of the inflammatory genes, iNOS, TNF-alpha, and IL-1beta, in macrophages stimulated by LPS. This effect was nearly comparable to that of cyclosporine A. This compound also significantly suppressed the production of nitric oxide and Th1-related pro-inflammatory cytokines, IL-1beta, TNF-alpha, and IL-2, with minimal suppression of Th2-related anti-inflammatory cytokines IL-4 and IL-10 in the sponge matrix allograft model. Moreover, administration of CT20126 prolonged the survival of allograft skins from BALB/c mice (H-2d) to the dorsum of C57BL/6 (H-2b) mice. The in vivo immune suppressive effects of CT20126 were similar to that of cyclosporine A. These results indicate that this compound may have potential therapeutic value for transplantation rejection and other inflammatory diseases.
Animals
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Cell Line
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Colchicine/*analogs & derivatives/chemistry/*pharmacology
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Cytokines/*biosynthesis
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Female
;
Gene Expression Regulation/drug effects
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Graft Survival/*drug effects
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Immunosuppression
;
Interleukin-1beta/genetics/metabolism
;
Lipopolysaccharides/pharmacology
;
Lymphocyte Culture Test, Mixed
;
Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Nitric Oxide/biosynthesis
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Nitric Oxide Synthase Type II/genetics/metabolism
;
Skin Transplantation/*immunology
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Th1 Cells/*drug effects/immunology/metabolism
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Th2 Cells/*drug effects/immunology/metabolism
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Transplantation, Homologous
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Tumor Necrosis Factor-alpha/genetics/metabolism
8.Two Case of Squamous cell Carcinoma of the Stomach in the Antrum.
Byung Suk PARK ; Hyung Guen LEE ; Oh Jung KWON ; Sung Joon KWON ; Kwang Soo LEE ; Kyu Young JUN ; Chi Kyu WON ; Jin Young KWAK ; Won Mee LEE ; Jung Dal LEE
Journal of the Korean Surgical Society 1997;52(5):760-765
Squamous cell carcinoma of the stomach is very rare with a reported incidence of 0.09% of all resected gastric malignancies. We report here two cases of squamous carcinomas and a brief review of literatures. A 74-year old female was admitted because of epigastric pain and vomiting. Abdominal CT, UGI and endoscopic findings revealed a Borrmann type III gastric cancer on the posterior wall of the antrum with pyrolic obstruction and multiple liver metastases. Palliative distal gastrectomy with gastrojejunostomy was performed. The histopathologic diagnosis was adenosquamous cell carcinoma. She died of malnutrition and multiple organ failure 5 months after the operation. The other case was a 53-year old male admitted because of indigestion. Abdominal CT, UGI and endoscopic findings revealed a Borrmann type III gastric cancer on the greater curvature of the antrum with multiple enlargements of the perigastric lymph nodes. Distal subtotal gastrectomy with gastrojejunistomy was performed. The histopathologic finding revealed squamous cell carcinoma. He was discharged after FEC(5-FU, etoposide, cispatin) chemotherapy uneventfully.
Aged
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Carcinoma, Squamous Cell*
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Diagnosis
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Drug Therapy
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Dyspepsia
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Etoposide
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Female
;
Gastrectomy
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Gastric Bypass
;
Humans
;
Incidence
;
Liver
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Lymph Nodes
;
Male
;
Malnutrition
;
Middle Aged
;
Multiple Organ Failure
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Neoplasm Metastasis
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Stomach Neoplasms
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Stomach*
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Tomography, X-Ray Computed
;
Vomiting
9.Nitric oxide suppresses inducible nitric oxide synthase expression by inhibiting post-translational modification of I kappa B.
Kwang CHANG ; Seon Jin LEE ; Ilyoung CHEONG ; Timothy R BILLIAR ; Hun Taeg CHUNG ; Jeong A HAN ; Young Guen KWON ; Kwon Soo HA ; Young Myeong KIM
Experimental & Molecular Medicine 2004;36(4):311-324
The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both normal physiological functions and the pathogenesis of disease. This study was undertaken to determine the molecular mechanism by which nitric oxide (NO) exerts negative feedback regulation on iNOS gene expression. Isolated rat hepatocytes stimulated with cytokines exhibited a marked increase in NO production as well as iNOS mRNA and protein levels, which were significantly reduced by pretreatment of the NO donors S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and V-PYRRO/NO. This effect of SNAP was inhibited when NO was scavenged using red blood cells. Pretreatment with oxidized SNAP, 8-Br-cGMP, NO2-, or NO3- did not suppress the cytokine-induced NO production. Moreover, LPS/ IFN-gamma-stimulated RAW264.7 cells, which produce endogenous NO, expressed lower levels of iNOS, IL-1beta, IL-6 and TNF-alpha mRNAs, without changes in their mRNA half-lives, than those in the presence of the iNOS inhibitor NG-monomethyl- L-arginine. The iNOS gene transcription rate exhibited an 18-fold increase after cytokine stimulation, which was significantly inhibited by SNAP pretreatment. SNAP also blocked cytokine- induced increase in NF-kappa B activation, iNOS promoter activity, nuclear translocation of cytosolic NF-kappa B p65 subunit, and I kappa B alpha degradation, which correlated with its inhibitory effect on phosphorylation and ubiquitination of I kappa B. These data indicate that NO down-regulates iNOS gene expression and NO production by inhibiting the post-translational processes of I kappa B alpha thereby preventing NF-kappa B activation. These results identify a novel negative feedback mechanism whereby NO down-regulates iNOS gene expression.
Animals
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Cell Line
;
Cell Nucleus/metabolism
;
Cyclic GMP/*analogs & derivatives/pharmacology
;
Cytokines/genetics/metabolism
;
*Down-Regulation
;
Hepatocytes/metabolism
;
I-kappa B/*metabolism
;
Lipopolysaccharides/pharmacology
;
Nitric Oxide/biosynthesis/*physiology
;
Nitric-Oxide Synthase/biosynthesis/*genetics
;
Penicillamine/*analogs & derivatives/pharmacology
;
Phosphorylation
;
Promoter Regions (Genetics)/genetics
;
*Protein Processing, Post-Translational
;
Protein Transport
;
Rats
;
Research Support, Non-U.S. Gov't
10.Arginase II inhibition prevents interleukin-8 production through regulation of p38 MAPK phosphorylation activated by loss of mitochondrial membrane potential in nLDL-stimulated hAoSMCs
Bon Hyeock KOO ; Bong Gu YI ; Myeong Seon JEONG ; Seung Hea KWON ; Kwang Lae HOE ; Young Guen KWON ; Moo Ho WON ; Young Myeong KIM ; Sungwoo RYOO
Experimental & Molecular Medicine 2018;50(2):e438-
Arginase inhibition exhibits beneficial effects in vascular endothelial and smooth muscle cells. In human aortic smooth muscle cells (hAoSMCs), native low-density lipoprotein (nLDL) induced the production of interleukin-8 (IL-8) that is involved in the pathogenesis of cardiovascular diseases. Therefore, we examined the effect of arginase inhibition on IL-8 production and the underlying mechanism. In hAoSMCs, reverse transcription–PCR, western blotting and immunocytochemistry with MitoTracker confirmed that arginase II was confined predominantly to mitochondria. The mitochondrial membrane potential (MMP) was assessed using tetramethylrhodamine ethyl ester. The MMP decreased upon nLDL stimulation but was restored upon arginase inhibition. MMP loss caused by nLDL was prevented by treatment with the intracellular Ca(2+) chelator BAPTA-AM. In mitochondrial Ca(2+) measurements using Rhod-2 AM, increased mitochondrial Ca(2+) levels by nLDL were inhibited upon preincubation with an arginase inhibitor. Among the polyamines, spermine, an arginase activity-dependent product, caused mitochondrial Ca(2+) movement. The nLDL-induced MMP change resulted in p38 mitogen-activated protein kinase (MAPK) phosphorylation and IL-8 production and was prevented by the arginase inhibitors BAPTA and ruthenium 360. In isolated AoSMCs from ApoE(−/−) mice fed a high-cholesterol diet, arginase activity, p38 MAPK phosphorylation, spermine and mitochondrial Ca(2+) levels and keratinocyte-derived chemokine (KC) production were increased compared with wild-type (WT) mice. However, in AoSMCs isolated from arginase II-null mice, increases in MMP and decreases in mitochondrial Ca(2+) levels were noted compared with WT and were associated with p38 MAPK activation and IL-8 production. These data suggest that arginase activity regulates the change in MMP through Ca(2+) uptake that is essential for p38 MAPK phosphorylation and IL-8 production.