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Biomedical subjects

Won Kim

Publications and source records attributed to Won Kim.

At least 55 records · Page 3Linked to original sources

Increased fasting plasma ghrelin levels during alcohol abstinence.

AIMS: Ghrelin is a peptide hormone that antagonizes the action of leptin and is thereby thought to regulate feeding behaviour. The actions of ghrelin and leptin appear to be mediated by the neuropeptide Y (NPY) and Agouti-related protein (AGRP) system. Recent studies have suggested that leptin and NPY play significant roles in the pathophysiology of alcoholism. The aim of this study was to determine whether ghrelin is associated with the state and duration of abstinence in individuals with alcohol dependence. METHODS: Fasting plasma ghrelin levels were compared between 47 individuals with chronic alcoholism during a period of abstinence and 50 control subjects. RESULTS: Fasting plasma ghrelin levels were higher in alcohol abstainers than those in controls. Furthermore, a positive correlation was observed between ghrelin levels and the duration of abstinence. In addition, daily alcohol intake prior to abstinence was inversely related to ghrelin levels. CONCLUSIONS: These findings suggest that ghrelin plays a role in the pathogenesis of alcohol dependence, particularly during the abstinence period, in individuals with chronic alcoholism.

Adult↗

LC-MS determination and bioavailability study of loperamide hydrochloride after oral administration of loperamide capsule in human volunteers.

The purpose of the present study was to develop a standard protocol for loperamide hydrochloride bioequivalence testing. For this purpose, a simple rapid and selective LC-MS method utilizing a single quadrupole mass spectrometer was developed and validated for the determination of loperamide hydrochloride in human plasma, and we followed this with a bioavailability study. Methyl tert-butylether (MTBE) was used to extract loperamide hydrochloride and ketoconazole (internal standard (IS)) from an alkaline plasma sample. LC separation was performed on a Zorbax RX C18 column (5 microm, 2.1 mm x 150 mm) using acetonitrile-water-formic acid (50:50:0.1 (v/v)) as a mobile phase. The retention times of loperamide hydrochloride and IS were 1.2 and 0.8 min, respectively. Quadrupole MS detection was by monitoring at m/z 477 (M + 1) corresponding to loperamide hydrochloride and at m/z 531 (M + 1) for IS. The described assay method showed acceptable precision, accuracy, linearity, stability, and specificity. The bioavailability of loperamide hydrochloride was evaluated in eight healthy male volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of four 2mg capsules of loperamide: the area under the plasma concentration versus time curve from time 0 to 72 h (AUC72 h) 19.26 +/- 7.79 ng h/ml; peak plasma concentration (Cmax) 1.18 +/- 0.37 ng/ml; time to Cmax (Tmax) 5.38 +/- 0.74 h; and elimination half-life (t1/2) 11.35 +/- 2.06 h. The developed method was successfully used to study the bioavailability of a low dose (8 mg) of loperamide hydrochloride.

Adult↗

COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity.

Angiopoietin-1 (Ang1) has potential therapeutic applications in inducing angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. However, production of Ang1 is hindered by aggregation and insolubility resulting from disulfide-linked higher-order structures. Here, by replacing the N-terminal portion of Ang1 with the short coiled-coil domain of cartilage oligomeric matrix protein (COMP), we have generated a soluble, stable, and potent Ang1 variant, COMP-Ang1. This variant is more potent than native Ang1 in phosphorylating the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor and Akt in primary cultured endothelial cells, enhancing angiogenesis in vitro and increasing adult angiogenesis in vivo. Thus, COMP-Ang1 is an effective alternative to native Ang1 for therapeutic angiogenesis in vivo.

Amino Acid Sequence↗

Designed angiopoietin-1 variant, COMP-Ang1, protects against radiation-induced endothelial cell apoptosis.

Radiation therapy is a widely used cancer treatment, but it causes side effects even when localized radiotherapy is used. Extensive apoptosis of microvascular endothelial cells of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Many in vitro studies suggest that angiopoietin-1 (Ang1) has potential therapeutic applications in enhancing endothelial cell survival. For in vivo use, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the Tie2 receptor in lung endothelial cells in vivo. Interestingly, COMP-Ang1 administered i.v. was mainly localized to microvascular endothelial cells of the intestinal villi and lung but not to microvascular endothelial cells of the liver. In irradiated mice, i.v. COMP-Ang1 protected against radiation-induced apoptosis in microcapillary endothelial cells of the intestinal villi and prolonged survival. Thus, COMP-Ang1 could be used as a therapeutic protein for specific protection against endothelial cell injury.

Angiopoietin-1↗

Glutathione S-transferase M1 polymorphism may contribute to schizophrenia in the Korean population.

The association between Glutathione S-Transferase M1 gene (GSTM1) polymorphism and schizophrenia was examined. One hundred and eleven in-patients with schizophrenia and 130 healthy controls were enrolled in this study. Genotyping was performed using a polymerase chain reaction-based method. The GSTM1 null genotype was significantly more frequent in the schizophrenia patients than in the controls (P=0.014, odds ratio=1.93, 95% confidence interval=1.115-3.351). On the other hand, the GSTM1 genotype variants were not associated with tardive dyskinesia or total abnormal involuntary movement scale scores. This study suggests that, at least in the Korean population, the GSTM1 polymorphism may confer susceptibility to the development of schizophrenia but not to tardive dyskinesia.

Adult↗

A case of unilateral renal cystic disease.

Unilateral renal cystic disease (URCD) is a distinct entity that is one of the renal cystic diseases. The clinical importance of URCD is to make a differential diagnosis from autosomal dominant polycystic kidney disease (ADPKD), multicystic dysplastic kidney, multilocular cystic renal neoplasm, and simple cysts. To confirm the diagnosis and to rule out asynchronous ADPKD requires long-term follow up, especially in younger patients.

Adult↗

Relationship of plasma Dendroaspis natriuretic peptide-like immunoreactivity and echocardiographic parameters in chronic haemodialysis patients.

BACKGROUND AND AIMS: The Dendroaspis natriuretic peptide (DNP), which was recently isolated from the venom of the green Mamba snake, Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure. The purpose of this study was to evaluate the effect of haemodialysis (HD) on the plasma concentration of DNP, and to investigate the relationship between the 2-D echocardiographic parameters and the changes in the plasma DNP levels during HD. METHODS: Forty-five haemodialysis patients and 22 healthy individuals underwent a measurement of plasma DNP-like immunoreactivity, serum creatinine, haematocrit, blood pressure and bodyweight before and after each HD session. Echocardiography was performed before and after HD. The peak early diastolic transmitral flow velocity (E), peak late diastolic transmitral flow velocity (A), and E/A ratio were measured by using a pulsed Doppler echocardiogram. RESULTS: The plasma DNP-like immunoreactivity of those in the pre-HD state was significantly higher (235.6 +/- 45.8 pg/mL) than those of the healthy subjects (105.3 +/- 31.1 pg/mL). In addition, the plasma DNP-like immunoreactivity was significantly decreased after HD (204.4 +/- 55.4 pg/mL). The left atrial diameter, left ventricular diameter at end diastole and end systol, E velocity, A velocity, E/A ratio and inferior vena cava diameter were significantly decreased after HD. There were significant correlations between the changes of plasma DNP-like immunoreactivity and the changes in the bodyweight and inferior vena cava diameter, respectively. CONCLUSION: These results suggest that the plasma DNP-like immunoreactivity might be involved in the regulation of the blood volume in patients undergoing HD.

Adult↗

Ectopic expression of a cecropin transgene in the human malaria vector mosquito Anopheles gambiae (Diptera: Culicidae): effects on susceptibility to Plasmodium.

Genetically altering the disease vector status of insects using recombinant DNA technologies is being considered as an alternative to eradication efforts. Manipulating the endogenous immune response of mosquitoes such as the temporal and special expression of antimicrobial peptides like cecropin may result in a refractory phenotype. Using transgenic technology a unique pattern of expression of cecropin A (cecA) in Anopheles gambiae was created such that cecA was expressed beginning 24 h after a blood meal in the posterior midgut. Two independent lines of transgenic An. gambiae were created using a piggyBac gene vector containing the An. gambiae cecA cDNA under the regulatory control of the Aedes aegypti carboxypeptidase promoter. Infection with Plasmodium berghei resulted in a 60% reduction in the number of oocysts in transgenic mosquitoes compared with nontransgenic mosquitoes. Manipulating the innate immune system of mosquitoes can negatively affect their capacity to serve as hosts for the development of disease-causing microbes.

Animals↗

Pacemaker lead endocarditis caused by Achromobacter xylosoxidans.

We report the case of a 35-yr-old patient who presented with high fever and chills. He had undergone a patch closure of the ventricular septal defect 18 yr before. One year later, a VVI pacemaker was implanted via the right subclavian vein because of complete heart block. Nine years after that, a new VVI pacemaker with another right ventricular electrode was inserted controlaterally and the old pacing lead was abandoned. Trans-thoracic and trans-esophageal echocardiogram identified the pacemaker lead in the right ventricle (RV) attaching hyperechoic materials and also a fluttering round hyperechoic mass with a stalk in the RV outflow tract. Cultures in blood and pus from pacemaker lead grew Achromobacter xylosoxidans. A diagnosis of pacemaker lead endocarditis due to Achromobacter xylosoxidans was made. In this regards, the best treatment is an immediate removal of the entire pacing system and antimicrobial therapy.

Achromobacter denitrificans↗

Comparison of proteome between hepatitis B virus- and hepatitis C virus-associated hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. Differential expression of the proteome in HBV- and HCV-associated HCC was investigated to identify any useful biomarkers indicating virus-specific hepatocarcinogenesis. EXPERIMENTAL DESIGN: Twenty-one pairs of specimens (tumorous and surrounding nontumorous liver tissues) were obtained from 21 HCC patients. They were divided into three HCC types by viral markers: 7 hepatitis B surface antigen-positive (B-type HCC), 7 anti-HCV-positive (C-type HCC), and 7 hepatitis B surface antigen-negative and anti-HCV-negative. Total proteins were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and alterations in the proteome were examined. RESULTS: Sixty proteins were identified that show significant changes in the expression level between nontumorous and tumorous tissues. Among these, 14 proteins were commonly changed in all three of the HCC types, but 46 proteins showed a tendency of viral marker specificity. CONCLUSIONS: The identified proteins were classified according to the viral factor as being involved in B-type and C-type HCC. These results suggest strongly that the expression pattern of proteome in HCC tissues is closely associated with etiologic factors. The different protein profiles between B-type and C-type HCC indicate that the pathogenetic mechanisms of hepatocarcinogenesis may be different according to the viral factor, HBV and HCV.

Carcinoma, Hepatocellular↗

Angiogenic role of adrenomedullin through activation of Akt, mitogen-activated protein kinase, and focal adhesion kinase in endothelial cells.

Adrenomedullin (AM) is a multifunctional peptide in human pheochromocytoma. To evaluate whether AM could be an angiogenic factor, we examined its effect on kinases and angiogenic processes. AM induced tyrosine phosphorylation of Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase1/2 (ERK1/2) by using distinct signaling pathways in human umbilical vein endothelial cells (HUVECs). AM also phosphorylated focal adhesion kinase, and phosphatidylinositol 3'-kinase inhibitor inhibited AM-induced focal adhesion kinase phosphorylation. Pretreatment with high concentrations of AM22-52, a putative AM receptor antagonist, partially suppressed AM-induced phosphorylation of Akt, ERK1/2, and focal adhesion kinase. AM and vascular endothelial growth factor produced increases in DNA synthesis and migration in HUVECs. AM induced tube formation in HUVECs, and its effect was inhibited by pretreatment with phosphatidylinositol 3'-kinase inhibitor or ERK1/2 inhibitor. AM induced sprouting in porcine pulmonary arterial endothelial cells and promoted neovessel formation in a mouse Matrigel plug assay. Inhibitors of phosphatidylinositol 3'-kinase and ERK1/2 inhibited AM-induced endothelial sprouting in vitro and angiogenesis in vivo. AM exerts angiogenic activity through activation of Akt, MAPK, and focal adhesion kinase in endothelial cells.

Adrenomedullin↗

Adrenomedullin reduces VEGF-induced endothelial adhesion molecules and adhesiveness through a phosphatidylinositol 3'-kinase pathway.

OBJECTIVE: In the initial phase of inflammation, vascular endothelial growth factor (VEGF) can act as a proinflammatory cytokine by inducing adhesion molecules that bind leukocytes to endothelial cells. Adrenomedullin (AM) is known to act as either a proinflammatory or an anti-inflammatory agent. In this study, we examined the effects of AM on adhesion molecule expression and leukocyte adhesiveness in VEGF-stimulated human umbilical vein endothelial cells. METHODS AND RESULTS: When stimulated with VEGF, the mRNAs of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were dose-dependently upregulated. AM inhibited the VEGF-induced protein and mRNA expression of ICAM-1, VCAM-1, and E-selectin. Phosphatidylinositol 3'-kinase inhibitor and a dominant-negative form of Akt significantly inhibited the suppressive effect of AM on VEGF-induced adhesion molecule expression. Thus, AM inhibits VEGF-stimulated ICAM-1 and VCAM-1 expression through a phosphatidylinositol 3'-kinase/Akt pathway. AM reduced VEGF-induced endothelial adhesiveness for leukocytes. CONCLUSIONS: These results suggest that AM might have an anti-inflammatory role in controlling VEGF-induced adhesion molecule gene expression and adhesiveness toward leukocytes in endothelial cells.

Adrenomedullin↗

Effects of alcohol hangover on cytokine production in healthy subjects.

A hangover is the syndrome of physical and mental symptoms that occurs 8 to 16 h after alcohol consumption with a zero level of alcohol. The aim of the current study was to investigate the effects of the alcohol hangover on cytokine production in healthy subjects. The hangover state was defined as 13 h after drinking 1.5 g/kg of alcohol (blood alcohol level=0). A venous blood sample was taken from 20 healthy adult men before consumption of alcohol and during the hangover state. Peripheral blood mononuclear cells were separated and stimulated with phytohemagglutinin. An enzyme-linked immunosorbent assay was used to measure the production of the following cytokines: interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We found that the concentrations of IL-10, IL-12, and IFN-gamma were significantly increased during the hangover state compared with the concentrations in normal conditions. These results support the suggestion that the dysregulated cytokine pathway (IL-10, IL-12, and IFN-gamma) is associated with the symptoms of hangovers.

Adult↗

Two Corbicula (Corbiculidae: Bivalvia) mitochondrial lineages are widely distributed in Asian freshwater environment.

We investigated the biogeography of Asian Corbicula using mitochondrial gene sequence variation for Corbicula members sampled from 24 localities of eight Asian regions. A total of 210 individuals were genetically characterized by examining sequence variations of a 614 bp fragment of the mitochondrial cytochrome oxidase I (COI) gene. Phylogenetic analyses of the COI dataset revealed that Corbicula members are subdivided into two well-supported clades: estuarine and freshwater. A robust dichotomy between the Japanese/Korean (Corbicula japonica) and Chinese (Corbicula fluminalis) estuarine forms was evident, suggesting that these two regional populations represent a deep phylogeographic split. Our mitochondrial gene tree showed that among the freshwater members, two Corbicula mitochondrial lineages are the most common, having attained extensive geographic distribution in the Asian freshwater environment. While the present study provides significant biogeographic information on Asian Corbicula, a comprehensive phylogenetic study by cross-referencing the mitochondrial-based Corbicula phylogeny with nuclear gene data is required to fully understand the evolutionary origin(s) of triploidy/clonality in this genus.

Animals↗

A new species of parastenhelia (Copepoda: Harpacticoida: Parastenheliidae) from Korea.

A new species belonging to the genus Parastenhelia of family Parastenheliidae is described on the basis of the specimens of both sexes collected from the zosteran bed at Seungbong Island and from the shallow sandy bottoms of Jeju Island in Korea. It is distinguished from the congeners by its character combination of inserted location and the length proportion of the inner seta on the first endopodal segment of leg 1, shape of female leg 5, the modified male legs 2-3 endopods, and the number of setae on male leg 5 exopod. An emended table of morphological characters for the genus is provided.

Animals↗