Biomedical subjects

Kwon-Ha Yoon

Publications and source records attributed to Kwon-Ha Yoon.

14 recordsLinked to original sources

PubMed2006

Anti-inflammatory activity of fisetin in human mast cells (HMC-1).

Mast cells play an important role in the pathogenesis of allergic diseases through the release of inflammatory mediators such as histamine, cysteinyl leukotrienes, cytokines, and chemokines. Flavonoids, like fisetin are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. The aim of our study was to examine whether fisetin modulates inflammatory reaction in stimulated human mast cells (HMC-1). Fisetin decreased phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated gene expression and production of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-4, IL-6, and IL-8 in HMC-1 cells. Fisetin inhibited PMACI-induced phosphorylation of p38 mitogen-activated protein kinase, extracellular-regulated kinase, and c-Jun N-terminal kinase. In addition, fisetin suppressed nuclear factor (NF)-kappaB activation induced by PMACI, leading to expression of IkappaB-alpha phosphorylation and degradation. Fisetin suppressed powerful induction of NF-kappaB promoter-mediated luciferase activity. These pharmacological actions of fisetin produce new suggestion that fisetin is a potential medicine for treatment of inflammatory diseases through the down-regulation of mast cell activation.

Anti-Inflammatory Agents↗

PubMed2006

COMP-angiopoietin-1 ameliorates renal fibrosis in a unilateral ureteral obstruction model.

Injury to the renal microvasculature may be a major factor in the progression of renal disease; therefore, protection of endothelial cells (EC) in renal vasculature may have a therapeutic role in renal fibrosis. Recently, a soluble, stable, and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, was developed. The contribution of COMP-Ang1 in renal interstitial fibrosis, however, remains to be clarified. This study investigated the effects of COMP-Ang1 on peritubular capillary EC in the renal cortex and the renal fibrogenic process that is triggered by unilateral ureteral obstruction. COMP-Ang1 preserved renal platelet-EC adhesion molecule-1-and Tie2-positive EC. Morphologic examination indicated less tubular injury and tubulointerstitial fibrosis in mice that received COMP-Ang1 than vehicle-treated mice. Interstitial type I collagen and myofibroblast accumulation were significantly suppressed by COMP-Ang1 treatment. COMP-Ang1 increased Tie2 and Akt phosphorylation in ureteral obstructed kidneys. Renal surface microvasculature and renal blood flow were higher after treatment with COMP-Ang1 than with vehicle. COMP-Ang1 treatment decreased monocyte/macrophage infiltration, tissue levels of TGF-beta1, and Smad 2/3 phosphorylation and increased Smad 7 in the obstructed kidney. These results demonstrate that COMP-Ang1 treatment can decrease the progression of renal fibrosis in unilateral ureteral obstruction. COMP-Ang1 may be an endothelium-specific therapeutic modality in fibrotic renal disease.

Angiopoietin-1↗

PubMed2006

Wolter type I x-ray focusing mirror using multilayer coatings.

A multilayer coating is a useful addition to a mirror in the x-ray region and has been applied to normal incidence mirrors used with soft x rays. When a multilayer coating is used on grazing incidence optics, higher performance can be achieved than without it. Cr/Sc multilayers coated on a Wolter type I mirror substrate for a soft x-ray microscope are considered. The reflectivity and effective solid angle are calculated for Wolter type I mirrors with uniform and laterally graded multilayer coatings. The laterally graded multilayer mirror showed superior x-ray performance, and the multilayer tolerances were relaxed. This multilayer mirror could be especially useful in the soft x-ray microscope intended for biological applications.

Journal Article↗

PubMed2006

Compact soft x-ray transmission microscopy with sub-50 nm spatial resolution.

In this paper, the development of compact transmission soft x-ray microscopy (XM) with sub-50 nm spatial resolution for biomedical applications is described. The compact transmission soft x-ray microscope operates at lambda = 2.88 nm (430 eV) and is based on a tabletop regenerative x-ray source in combination with a tandem ellipsoidal condenser mirror for sample illumination, an objective micro zone plate and a thinned back-illuminated charge coupled device to record an x-ray image. The new, compact x-ray microscope system requires the fabrication of proper x-ray optical devices in order to obtain high-quality images. For an application-oriented microscope, the alignment procedure is fully automated via computer control through a graphic user interface. In imaging studies using our compact XM system, a gold mesh image was obtained with 45 nm resolution at x580 magnification and 1 min exposure. Images of a biological sample (Coscinodiscus oculoides) were recorded.

Diatoms↗

PubMed2006

Gliotoxin reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice: evidence of the connection between heme oxygenase-1 and the nuclear factor-kappaB pathway in vitro and in vivo.

BACKGROUND: Gliotoxin, a fungal metabolite, has been known to show strong immunosuppressive properties, although its mechanisms are not completely understood. In this report, the authors investigated the mechanism whereby gliotoxin has anti-inflammatory properties in vitro and in trinitrobenzene sulfonic acid-induced colitis. MATERIALS AND METHODS: Body weight, histological scores, and myeloperoxidase activity were evaluated in trinitrobenzene sulfonic acid colitis. Nuclear factor-kappaB (NF-kappaB) p65, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-12, and intercellular adhesion molecule-1 were detected by immunohistochemical staining. IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Heme oxygenase-1 (HO-1) expression and I-kappaB degradation were analyzed by Western blot. RESULTS: Pretreatment of human epithelial HT-29 cells with gliotoxin significantly blocked the I-kappaB degradation and NF-kappaB p65 nuclear translocation induced by tumor necrosis factor-alpha or IL-1beta; these were parallel with the inhibition of IL-8 secretion and intercellular adhesion molecule-1 expression in the same cells. Interestingly, gliotoxin induced HO-1 in HT-29 cells and, in turn, inhibition of HO-1 activity by a zinc protoporphyrin IX reversed the effects of gliotoxin in terms of I-kappaB degradation, intercellular adhesion molecule-1 expression, and IL-8 production. In trinitrobenzene sulfonic acid colitis, gliotoxin administration significantly improved the clinical and histopathological symptoms. Notably, gliotoxin also induced HO-1 in the colonic mucosa and zinc protoporphyrin IX reversed the protective effects of gliotoxin in trinitrobenzene sulfonic acid colitis. CONCLUSIONS: These results demonstrate for the first time that the anti-inflammatory actions mediated by gliotoxin include HO-1 induction and the subsequent blockade of NF-kappaB-dependent signaling pathways in vitro and in vivo. The current results also demonstrate that gliotoxin may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

Animals↗

PubMed2004

Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways.

Competition for cellular iron (Fe) is a vital component of the interaction between host and pathogen. Most bacteria have an obligate requirement for Fe to sustain infection, growth, and survival in host. To obtain iron required for growth, many bacteria secrete iron chelators (siderophores). This study was undertaken to test whether a bacterial siderophore, deferoxamine (DFO), could trigger inflammatory signals in human intestinal epithelial cells as a single stimulus. Incubation of human intestinal epithelial HT-29 cells with DFO increased the expression of IL-8 mRNA, as well as the release of IL-8 protein. The signal transduction study revealed that both p38 and extracellular signal-regulated kinase-1/2 were significantly activated in response to DFO. Accordingly, the selective inhibitors for both kinases, either alone or in combination, completely abolished DFO-induced IL-8 secretion, indicating an importance of mitogen-activated protein kinases pathway. These proinflammatory effects of DFO were, in large part, mediated by activation of Na(+)/H(+) exchangers, because selective blockade of Na(+)/H(+) exchangers prevented the DFO-induced IL-8 production. Interestingly, however, DFO neither induced NF-kappaB activation by itself nor affected IL-1beta- or TNF-alpha-mediated NF-kappaB activation, suggesting a NF-kappaB-independent mechanism in DFO-induced IL-8 production. Global gene expression profiling revealed that DFO significantly up-regulates inflammation-related genes including proinflammatory genes, and that many of those genes are down-modulated by the selective mitogen-activated protein kinase inhibitors. Collectively, these results demonstrate that, in addition to bacterial products or cell wall components, direct chelation of host Fe by infected bacteria may also contribute to the evocation of host inflammatory responses.

Deferoxamine↗

PubMed2003

Identification of novel polymorphisms in the Adam33 gene.

Adam33 is a member of a family of genes that encode membrane-anchored proteins with a disintegrin and a metalloprotease domain and that are primarily expressed in lung fibroblasts and bronchial smooth muscle. The human Adam33 gene is located on chromosome 20p13, a region that has been linked to asthma and bronchial hyperresponsiveness. Recently, the polymorphisms in Adam33 have been found to be associated with asthma. In this study, we performed polymorphism scanning of the entire genomic region, including the promoter region of Adam33, by direct sequencing. We identified 16 novel polymorphisms in the Adam33 gene. Among these novel polymorphisms, three polymorphisms (-2154G-->A, -753T-->A, and -330C-->T) were found to be in the promoter region and one polymorphism (13491 G-->A) was located in 3' untranslated region of the Adam33 gene.

3' Untranslated Regions↗

PubMed2003

Soluble factor from murine bladder tumor-2 cell elevates nitric oxide production in macrophages and enhances the taxol-mediated macrophage cytotoxicity on tumor cells.

The therapeutic mechanism of taxol is believed to reside primarily in its ability to stabilize microtubules and prevent cell progression through mitosis. Taxol also can activate macrophage-mediated antitumor mechanism through a nitric oxide (NO)-dependent pathway. To address whether any mechanisms account for superficial urinary bladder tumor cell killing, we evaluated the effects of taxol on the growth and viability of murine bladder tumor-2 (MBT-2) cells in vitro, both in the absence and presence of murine macrophages. In addition, we evaluated whether a soluble factor generated from MBT-2 cells could modulate the antitumor activity of the taxol-activated macrophages. Although taxol inhibited the growth of MBT-2 cells, it did not kill the tumor cells. However, preincubation of macrophages with taxol significantly decreased the viability of MBT-2 cells. Secretion of NO correlated with MBT-2 cell killing, and the activated macrophages failed to kill tumor cell targets in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of NO synthase. By the co-culture of macrophages and MBT-2 cells, untreated macrophages also released modest amount of NO and this was synergistically augmented by the treatment with taxol, indicating that MBT-2 tumor cells released some unknown factor that activated the macrophages and enhanced NO production. We named this factor the tumor-derived macrophage activating factor (TMAF). The TMAF-mediated activation of macrophages to enhance the NO production was not blocked by treatment of macrophages with oxidized low-density lipoprotein (Ox-LDL), implying that the scavenger receptor of macrophages is not involved. Sodium nitroprusside (SNP), an NO donor given to the MBT-2 cells, increased the activities of c-Jun N-terminal kinase and caspase-3 in MBT-2 cells and associated with nucleosomal fragmentation or apoptosis, whereas taxol had no direct effect on these parameters. Collectively, our results strongly suggest that taxol kills the murine bladder tumor cells through indirect activation of macrophages via NO-dependent apoptosis, instead of its better-known role as the direct antimitotic action. Our results further demonstrate that TMAF acts in synergy with taxol to activate the macrophages to elicit enhanced tumor cell killing ability.

Animals↗

PubMed2002

Involvement of p38 MAP kinase during iron chelator-mediated apoptotic cell death.

Iron is an essential element for the neoplastic cell growth, and iron chelators have been tested for their potential anti-proliferative and cytotoxic effects. To determine the mechanism of cell death induced by iron chelators, we explored the pathways of the three structurally related mitogen-activated protein (MAP) kinase subfamilies during apoptosis induced by iron chelators. We report that the chelator deferoxamine (DFO) strongly activates both p38 MAP kinase and extracellular signal-regulated kinase (ERK) at an early stage of incubation, but slightly activates c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) at a late stage of incubation. Among three MAP kinase blockers used, however, the selective p38 MAP kinase inhibitor SB203580 could only protect HL-60 cells from chelator-induced cell death, indicating that p38 MAP kinase serves as a major mediator of apoptosis induced by iron chelator. DFO also caused release of cytochrome c from mitochondria and induced activation of caspase 3 and caspase 8. Interestingly, treatment of HL-60 cells with SB203580 greatly abolished cytochrome c release, and activation of caspase 3 and caspase 8. Collectively, the current study reveals that p38 MAP kinase plays an important role in iron chelator-mediated cell death of HL-60 cells by activating downstream apoptotic cascade that executes cell death pathway.

Animals↗

PubMed2002

Prognostic value of CT before thrombolytic therapy in iliofemoral deep venous thrombosis.

PURPOSE: To prospectively assess the computed tomographic (CT) findings of iliofemoral deep venous thrombosis (DVT) and evaluate their relevance to the treatment of DVT with catheter-directed thrombolysis. MATERIALS AND METHODS: Twenty-four consecutive patients with symptomatic iliofemoral DVT were studied with both nonenhanced and contrast-enhanced CT before thrombolytic therapy. Mean duration of clinical symptom was 15.8 days +/- 20.8 (range, 1-90 d). Selected CT findings were prospectively evaluated and correlated with duration of symptoms and outcome of thrombolytic therapy, including attenuation number of the thrombus on nonenhanced CT (in HU), presence of venous distention (distention ratio: vein diameter divided by the diameter of corresponding normal contralateral vein), and poor venous wall demarcation. The following threshold variables were also evaluated: attenuation > or =60 HU and distention ratio > or =1.5. RESULTS: CT was suggestive of DVT in all patients, although different patterns were present. Higher attenuation on noncontrast CT was seen in patients who had favorable outcome of thrombolytic therapy compared to poor responders (66.1 +/- 8.7 vs 45.9 +/- 9.6; P <.0001). Distention ratio was also significantly higher in the good response group (2.6 +/- 1.4 vs 1.4 +/- 0.7; P <.05). Recent onset of clinical symptoms was associated with better outcome (9.4 d +/- 8.9 vs 28.6 d +/- 31.2; P <.03). Multiple-stepwise regression analysis of these variable produce the results of "attenuation >60" as the most predictive variable of favorable outcome of thrombolysis, followed by "distention ratio >1.5" and poor demarcation. CONCLUSION: Selected CT findings are better predictors of a favorable outcome of thrombolytic therapy than duration of clinical symptoms alone.

Adult↗

PubMed2002

MR evaluation of the "arcuate" sign of posterolateral knee instability.

OBJECTIVE: The purpose of this study was to evaluate associated knee injuries using MR imaging in patients with the "arcuate" sign, a term referring to avulsion fracture of the proximal fibula on conventional radiographs. MATERIAL AND METHODS: MR imaging of 18 cases (17 patients, both knees in one patient) with the arcuate sign on conventional radiographs was retrospectively interpreted to evaluate the associated meniscal, ligamentous, and bony injuries. In 12 cases, MR findings were correlated with surgical results. RESULTS: In all cases, avulsed bony fragments from the proximal pole of the fibula were attached to the fibular collateral ligament, the biceps femoris tendon, or both. Tear of the posterolateral capsule was seen in 12 cases (67%). Injury of the cruciate ligaments was noted in 16 cases (89%): injury to both the anterior cruciate ligament and posterior cruciate ligament was seen in nine cases (50%), injury to only the anterior cruciate ligament was seen in four, and injury to the posterior cruciate ligament only was noted in three. Bone bruises or gross fractures were seen in all cases: bone bruises on the anteromedial femoral condyle were noted in nine cases (50%) and were seen on the anteromedial tibial condyle in five cases (28%). Tear of the medial meniscus was seen in five cases (28%) and tear of the lateral meniscus in four cases (22%). Injury to the popliteus was seen in six cases (33%). Joint effusion was associated in all cases. CONCLUSION: MR imaging is useful for evaluation of associated soft-tissue injuries in patients with the arcuate sign on conventional radiographs. Avulsion injury to the proximal fibula is an important indicator of the internal derangement of the knee and for predicting the mechanism of an injury with varus stress. Cruciate ligament tear and bone bruises on the anteromedial condyle of the femur and tibia are common associated findings.

Adult↗

PubMedDate not supplied

Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings.

Although radio-frequency (RF) ablation has been accepted as a promising and safe technique for treatment of unresectable hepatic tumors, investigation of its complications has been limited. According to the multicenter (1,139 patients in 11 institutions) survey data of the Korean Study Group of Radiofrequency Ablation, a spectrum of complications occurred after RF ablation of hepatic tumors. The prevalence of major complications was 2.43%. The most common complications were hepatic abscess (0.66%), peritoneal hemorrhage (0.46%), biloma (0.20%), ground pad burn (0.20%), pneumothorax (0.20%), and vasovagal reflex (0.13%). Other complications were biliary stricture, diaphragmatic injury, gastric ulcer, hemothorax, hepatic failure, hepatic infarction, renal infarction, sepsis, and transient ischemic attack. One procedure-related death (0.09%) occurred (due to peritoneal hemorrhage). Three important strategies for decreasing the rate of complications are prevention, early detection, and proper management. A physician who performs RF ablation of hepatic malignancies should be aware of the broad spectrum of major complications so that these strategies can be used.

Aged↗

PubMedDate not supplied

Intraductal papillary mucinous tumor of the bile ducts.

Papillary tumors of the bile ducts are intraductal tumors with numerous minute frondlike papillary projections. Some intraductal papillary tumors of the bile ducts produce a large amount of mucin that disturbs bile flow and causes severe biliary dilatation. In the presence of a tumor of this subgroup, the entire biliary tree is dilated; segmental or lobar bile ducts are dilated disproportionately, and aneurysmal dilatation may occur. Mucin is depicted at cholangiography as multiple elongated or cordlike filling defects, and the tumor is depicted on cross-sectional images as a castlike, polypoid, or fungating mass in the dilated biliary tree. Based on these characteristic imaging features-dilatation, mucin, and tumor-correct diagnosis of intraductal papillary mucinous tumor of the bile ducts may be made.

Adenocarcinoma, Papillary↗

PubMedDate not supplied

Focal hepatic lesions: contrast-enhancement patterns at pulse-inversion harmonic US using a microbubble contrast agent.

OBJECTIVE: To analyze the contrast-enhancement patterns obtained at pulse-inversion harmonic imaging (PIHI) of focal hepatic lesions, and to thus determine tumor vascularity and the acoustic emission effect. MATERIALS AND METHODS: We reviewed pulse-inversion images in 90 consecutive patients with focal hepatic lesions, namely hepatocellular carcinoma (HCC) (n=43), metastases (n=30), and hemangioma (n=17). Vascular and delayed phase images were obtained immediately and five minutes following the injection of a microbubble contrast agent. Tumoral vascularity at vascular phase imaging and the acoustic emission effect at delayed phase imaging were each classified as one of four patterns. RESULTS: Vascular phase images depicted internal vessels in 93% of HCCs, marginal vessels in 83% of metastases, and peripheral nodular enhancement in 71% of hemangiomas. Delayed phase images showed inhomogeneous enhancement in 86% of HCCs; hypoechoic, decreased enhancement in 93% of metastases; and hypoechoic and reversed echogenicity in 65% of hemangiomas. Vascular and delayed phase enhancement patterns were associated with a specificity of 91% or greater, and 92% or greater, respectively, and with positive predictive values of 71% or greater, and 85% or greater, respectively. CONCLUSION: Contrast-enhancement patterns depicting tumoral vascularity and the acoustic emission effect at PIHI can help differentiate focal hepatic lesions.

Adult↗